ABSTRACT
Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting over 50 million people worldwide in 2020 and this number will triple to 152 million by 2050. Much of the increase will be in developing countries like Colombia. In familial forms, highly penetrant mutations have been identified in three genes, APP, PSEN1, and PSEN2, supporting a role for amyloid-ß peptide. In sporadic forms, more than 30 risk genes involved in the lipid metabolism, the immune system, and synaptic functioning mechanisms. We used whole-exome sequencing (WES) to evaluate a family of 97 members, spanning three generations, with a familiar AD, and without mutations in APP, PSEN1, or PSEN2. We sequenced two affected and one unaffected member with the aim of identifying genetic variants that could explain the presence of the disease in the family and the candidate variants were validated in eleven members. We also built a structural model to try to determine the effect on protein function. WES analysis identified two rare variants in SORL1 and MTHFD1L genes segregating in the family with other potential risk variants in APOE, ABCA7, and CHAT, suggesting an oligogenic inheritance. Additionally, the structural 3D models of SORL1 and MTHFD1L variants shows that these variants produce polarity changes that favor hydrophobic interactions, resulting in local structural changes that could affect the protein function and may contribute to the development of the disease in this family.
Subject(s)
Alzheimer Disease , Aged , Humans , Alzheimer Disease/genetics , Amyloid beta-Protein Precursor/genetics , Colombia , Exome Sequencing , Genetic Predisposition to Disease , LDL-Receptor Related Proteins/genetics , Membrane Transport Proteins/genetics , Mutation , Presenilin-1/geneticsABSTRACT
Insulin resistance and defects in other related glycemic traits are common findings in the context of Metabolic Syndrome. Although genetic factors are clearly implied in susceptibility, and some gene variants have been identified mainly in populations of European ancestry, little is known about this aspect in admixed populations. The association of insulin resistance, ß-cell function, fasting insulin and glucose levels with 48 gene variants, previously related to metabolic syndrome components, and with the ancestral genetic composition, estimated on 50 ancestry informative markers, was evaluated in 417 individuals from the Colombian admixed population. The Native American genetic ancestry was associated with a low ß-cell function (odds ratio (OR) of 1.73 and 95% confidence interval (95% CI) of 1.07-2.81, pâ¯=â¯0.026). Significant genotypic associations were obtained (q-valueâ¯<â¯0.05) for gene variants in ACE (rs4340; OR (95% CI): 2.79 (1.58-4.91), insulin resistance; mean difference (95% CI): 0.273 (0.141; 0.406), fasting insulin), ADIPOR2 (rs11061971; OR (95% CI): 0.14 (0.04-0.48), low ß-cell function), MTNR1B (rs10830963; mean difference (95% CI): 0.032 (0.013; 0.051), fasting glucose) and GCK (rs4607517; mean difference (95% CI): 0.038 (0.020;0.056) and rs1799884; mean difference (95% CI): 0.027 (0.013-0.041), fasting glucose). Also the well-known gene variants rs7903146 in TCF7L2, and rs17817449 in FTO, were nominally associated with hyperglycemia (rs7903146), as well as with higher fasting insulin levels (rs17817449). Our findings indicate that gene variants in ACE, ADIPOR2, MTNR1B, GCK, TCF7L2 and FTO, are associated with glycemic traits in the admixed Colombian population, while a higher Native American genetic component is related to lower ß-cell function.
Subject(s)
Genetic Variation/genetics , Glycemic Index/genetics , Indians, North American/genetics , Proteins/genetics , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Colombia , Female , Genotype , Germinal Center Kinases , Humans , Insulin Resistance/genetics , Male , Peptidyl-Dipeptidase A/genetics , Protein Serine-Threonine Kinases/genetics , Receptor, Melatonin, MT2/genetics , Receptors, Adiponectin/genetics , Transcription Factor 7-Like 2 Protein/genetics , Young AdultABSTRACT
BACKGROUND AND OBJECTIVE: Insulin resistance (IR) is a condition favored by metabolic and endocrine changes experienced by adipose tissue in the context of obesity. The prevalence and the presentation of both IR and obesity vary among the populations, and may be affected by ancestral genetic composition among other factors. The aim of this study was to compare the presence of IR and obesity in Amerindians of the Embera-Chamí ethnicity and Colombian mestizo population. PATIENTS AND METHODS: A sample of 630 individuals, 471 mestizos and 159 Amerindians of the Embera-Chamí ethnicity, from the general population of Colombia were studied. For each participant, anthropometric and biochemical measurements, as well as blood pressure and the Homeostatic Model Assessment (HOMA) of IR and ß-cell function (%B) were recorded. These values were compared between the two populations. RESULTS: While prevalence of central obesity was similar in both populations (48.7% and 42.6% in the mestizo and Embera groups respectively; p=0.148), body mass index (BMI) values suggested a higher prevalence of overweight in the Embera than in mestizo population (43.4% Embera, 31.8% mestizo; p=0.027). Despite the similarities in the prevalence of HOMA-IR and HOMA-%B status between both populations, the Embera population had a significantly greater pancreatic ß-cell function, higher insulin levels, and better glucose control, across BMI and central obesity categories, than the mestizo population. CONCLUSION: There are differences in aspects related to energy metabolism between the samples of the mestizo and Amerindian populations analyzed.
Subject(s)
Adiposity/ethnology , Ethnicity/statistics & numerical data , Indians, South American/statistics & numerical data , Insulin Resistance/ethnology , Adolescent , Adult , Anthropometry , Blood Glucose/analysis , Blood Pressure , Child , Colombia/epidemiology , Cross-Sectional Studies , Energy Metabolism , Humans , Insulin/blood , Insulin-Secreting Cells/physiology , Marriage , Metabolic Syndrome/ethnology , Middle Aged , Obesity, Abdominal/ethnology , White People , Young AdultABSTRACT
OBJECTIVE: To determine the allelic and genotype frequencies of apolipoproteine E (APOE) gene in a representative sample of the adult population of Medellin in 2010. METHODS: A representative sample of the adult population of Medellin, was obtained by means of a multi-stage, stratified, conglomerate based sampling method. APOE genotyping was carried out on each of the participants. The sampling design was taken into consideration for the frequencies and association analysis. RESULTS: The frequencies of the APOE alleles E2, E3 and E4 were 3.9, 92.0 and 4.1%, respectively. The frequencies of the different APOE genotypes were as follows: 2/2, 0.2%; 2/3, 6.8%; 2/4, 0.6%; 3/3, 85.0%; 3/4, 7.2%, and 4/4, 0.3%. CONCLUSIONS: The allelic and genotype frequencies of APOE in an adult population of Medellin did not differ substantially from other series reported in South America. These data are important to determine the real impact of APOE on the population risk of several psychiatric diseases.
ABSTRACT
Resumen Objetivo: Analizar la prevalencia de los desórdenes venosos crónicos (dvc) en los embera-chamí de Cristianía (Karmata Rua), en el suroeste de Antioquia, y conocer sus posibles factores asociados (fa). Metodología: Estudio de corte de una muestra aleatoria de 488 sujetos. El diagnóstico se realizó mediante ecoduplex venoso. Se recolectó información sobre fa sociodemográficos, comportamentales y antropométricos. Los fa más relevantes se seleccionaron por regresión logística binaria múltiple. Resultados: La prevalencia de várices fue del 27,5 % y la de insuficiencia venosa crónica (ivc) del 0,8 %. Hubo compromiso de segmentos anatómicos superficiales en el 34,8 % de los individuos. La edad fue el fa más importante, con Odds Ratio (or) entre 3,33 y 6,30 según el tipo de dvc (excepto C1). El sexo femenino, la paridad, la grasa en el muslo y pierna y la talla alta se asociaron a telangiectasias. La edad, la grasa abdominal y la forma de la pierna fueron fa de várices. A las venas superficiales, en ambos sexos, se asociaron la edad y la grasa abdominal y, en mujeres, también los antecedentes familiares de várices. A las profundas y perforantes se asociaron la edad y la depleción de grasa periférica. Conclusiones: El patrón de baja prevalencia de los dvc en embera-chamí puede ser consecuencia de los estilos de vida relacionados con la actividad física diaria y las diferencias genéticas compartidas con amerindios. En los programas de atención en salud diferencial deberían considerarse los desórdenes profundos y perforantes respecto a mestizos.
Abstract Objective: To analyze the prevalence of chronic venous disorders (CVD) in the embera-chamí from Cristianía (Karmata Rua), in the southwest of Antioquia, and to study possible associated factors (AF). Methodology: A cross sectional study of a random sample of 488 subjects. The diagnosis was performed through Doppler ultrasonography. Information about sociodemographic, behavioral and anthropometric AFs was collected. The most relevant AFs were selected through multiple binary logistic regression. Results: The prevalence of varicose veins was 27.5% and that of chronic venous insufficiency (cvi) was 0.8%. Superficial anatomical segments were compromised in 34.8% of individuals. Age was the most important AF, with an Odds Ratio (OR) between 3.33 and 6.30 according to the type of cvd. Being a female, parity, fat in the thigh/leg and large size were associated with telangiectasias. Age, abdominal fat and leg shape were AF of varicose veins. Superficial veins in both sexes were associated with age and abdominal fat and in women, also with a family background of varicose veins. Deep and perforator veins were associated with age and peripheral fat depletion. Conclusions: The low prevalence pattern of CVDs in embera-chamí may be a consequence of lifestyles involving daily physical activity and genetic differences shared with Amerindians. Deep and perforating disorders should be considered in differential health care programs in relation to mestizos.
Resumo Objetivo: Analisar a prevalência de doenças venosas crônicas (dvc) na Embera-Chami Christiania (KarmataRua), no sudoeste do estado de Antioquia, e conhecer seus fatores associados (AF). Metodologia: Um estudo de coorte de uma amostra aleatória de 488 indivíduos. O diagnóstico foi feito por ecoduplex venoso. Informações sobre FA sócio demográficas, comportamentais e antropométricas foram coletadas. Os FAs mais relevantes foram selecionados para múltipla regressão logística binária. Resultados: A prevalência de varizes foi de 27,5% e a de insuficiência venosa crônica (ivc) foi de 0,8%. Houve comprometimento dos segmentos anatômicos superficiais em 34,8% dos indivíduos. A idade foi a FA mais importante, com Odds Ratio (OR) entre 3,33 e 6,30 de acordo com o tipo de dvc. Sexo feminino, paridade, gordura na coxa e perna e altura foram associados a telangiectasias. Idade, gordura abdominal e formato de perna foram FA de varizes. Nas veias superficiais, em ambos os sexos, idade e gordura abdominal estavam associadas e, nas mulheres, também a história familiar de varizes. Às profundas e perfurantes foram associadas a idade e depleção de gordura periférica. Conclusões: O padrão de baixa prevalência de DVC em embera-chamí pode ser uma consequência de estilos de vida relacionados à atividade física diária e diferenças genéticas compartilhadas com ameríndios. Em programas diferenciais de atenção à saúde, distúrbios profundos e perfurantes devem ser considerados em relação aos mestiços.
ABSTRACT
Increased prevalence of obesity in the world, especially accumulation of abnormal amounts of visceral fat predisposes to insulin resistance, which is the central role of metabolic syndrome (MS). Obesity can deregulate the intracellular signaling of insulin due to the production of inflammatory substances, chemoattractant proteins, adipokines and molecules that trigger hormonal mediator potentials for destabilization of signal transduction, leading to metabolic disorders such as hyperglycemia, hypertension, and dyslipidemia. The complexity of the MS and of the genetic mechanisms involved in its etiology derives from the combination of variants on genes involved and environmental factors that predispose it. The purpose of this paper is to review the effects of obesity in molecular and biochemical responses that trigger insulin resistance and its relation to some candidate genes and the ancestral component of the population.
El aumento en la prevalencia de la obesidad en el mundo, especialmente el acumulo de grasa visceral, predispone a resistencia a la insulina, eje central del Síndrome metabólico (SM). La obesidad puede desregular la señalización intracelular de la insulina debido a la producción de sustancias inflamatorias, proteínas quimioatrayentes, adipoquinas y mediadores hormonales que activan moléculas potenciales para la desestabilización de la transducción de la señal, lo que genera alteraciones metabólicas como hiperglucemia, hipertensión y dislipidemia. La complejidad del SM y de los mecanismos genéticos involucrados en su etiología, se deriva de la combinación entre variantes génicas implicadas y factores del medioambiente que la predisponen. El propósito del presente artículo es revisar los efectos de la obesidad en las respuestas moleculares y bioquímicas que desencadenan resistencia a la insulina y su relación con algunos genes candidatos y el componente ancestral de la población.
ABSTRACT
INTRODUCTION: Polymorphisms in promoters of genes code for cytokines that affect transcription levels. Several have been associated with leprosy patients that have functional and clinical implications. OBJECTIVE: Polymorphisms in the promoter of the IL10 gene of leprosy patients will be compared frequencies in normal population. MATERIALS AND METHODS: SNPs (single nucleotide polymorphism) -1082 A/G (rs1800896), -819C/T (rs1800871), and -592A/C (rs1800872) were identified in 100 leprosy patients and in a control group of 100 volunteers from a leprosy endemic region of Colombia. RESULTS: The genotypes C/C and C/T in the SNP -819 were associated together with leprosy (OR=4.34, p<0.001).Similarly, the genotypes C/C and C/A in the -592 SNP showed an association (OR=4.3, p<0.001). The haplotypes -819C-519C and -1082A-819C-592C showed significant association (OR=4.34, p<0.001 and OR=6.25, p<0.001) respectively. These haplotypes in homozygosis conditions were also associated with leprosy: -819C-519C/-819C-519C (OR=4.34, p<0.001), -1082A -819C-592C/-1082A -819C-592C (OR=1.90, p=0.04). The SNP -1082 was not associated with leprosy in this population. CONCLUSIONS: The haplotypes associated with leprosy, -1082A-819C-592C/-1082A-819C-592C, have been reported as low producers of IL-10. Functionally, the low production of IL-10 may have immune response consequences and clinical implications. Additional haplotypes of IL-10 have been reported as markers for leprosy susceptibility or resistance in other ethnic populations. This suggests that differences in distribution of diverse IL-10 gene polymorphisms among ethnic groups may indicate important gene-disease associations.
Subject(s)
Interleukin-10/genetics , Leprosy/genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Colombia/epidemiology , Endemic Diseases , Ethnicity/genetics , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Haplotypes , Humans , Interleukin-10/biosynthesis , Interleukin-10/physiology , Leprosy/epidemiology , Leprosy/microbiology , Male , Middle Aged , Mycobacterium leprae/isolation & purification , White People/genetics , Young AdultABSTRACT
Estudiamos la prevalencia de los factores de riesgo cardiovascular en 488 individuos mayores de 14 años, en el resguardo indígena Karmata Rúa de Cristianía. Se encontraron las siguientes frecuencias: hipertensión arterial (HTA) 18,1%; antecedente personal de diabetes mellitus 3,3%; glucemia mayor de 126 mg/dL 0,7%; hábito de fumar 15%; sobrepeso 40,2%; obesidad 8,0%; hipercolesterolemia 21,4%; hipertrigliceridemia 33,3% y dislipidemia 56,2%. El índice de masa corporal y los valores de colesterol total, glucemia, perímetro de la cintura, índice cintura/ cadera y presión arterial sistólica y diastólica presentaron correlación positiva y significativa con la edad. El grado de escolaridad mostró correlación negativa con el perímetro de la cintura, el índice cintura/cadera, la glucemia y la presión arterial. Al comparar con poblaciones indígenas y no indígenas de Colombia y de otros países, se encontró una prevalencia entre tres y cuatro veces menor de diabetes mellitus; en la población estudiada hay menos HTA aunque existe tendencia al sobrepeso. No se encontraron diferencias significativas en otros factores de riesgo; todos ellos fueron más frecuentes en mujeres, en personas de escolaridad baja y en individuos mayores. Los factores que contribuyen a estas diferencias son genéticos (homogeneidad étnica) y ambientales, como la mayor actividad física de los hombres, la dieta y la estructura demográfica.
Prevalence of cardiovascular risk factors was studied in 488 individuals over the age of 14 years in the Karmata Rua indigenous population of Cristianía, Colombia. The following rates were found: arterial hypertension 18.1%, family history of diabetes mellitus 3.3%, serum glucose over 126 mg/dL 0.7%, smoking habit 15%, overweight 40.2%, obesity 8.0%, hypercholesterolemia 21.4%, hypertriglyceridemia 33.3% and dyslipidemia 56.2%. Values of body mass index, total cholesterol, glucose, waist circumference, waist/hip index, systolic and diastolic blood pressure showed a positive and significant correlation with age. Higher level of education showed negative correlation with waist circumference, the waist/hip index, blood sugar and blood pressure. In comparison with other indigenous and non-indigenous communities of Colombia and other countries, prevalence of diabetes mellitus was between three and four times lower in the studied population; prevalence or high blood pressure was also lower despite a tendency to overweight. For other risk factors no significant differences were found, but they were more common in women, in people with low level of schooling and in elder individuals. Probably this difference is caused by genetic and environmental factors, such as increased physical activity in men, diet, and population structure.
Estudamos a prevalência dos fatores de risco cardiovascular em 488 indivíduos maiores de 14 anos, no resguardo indígena Karmata Rúa de Cristianía. Encontraram- se as seguintes frequências: hipertensão arterial (HTA) 18,1%; antecedente pessoal de diabete mellitus 3,3%; glicemia maior de 126 mg/DL 0,7%; hábito de fumar 15%; sobrepeso 40,2%; obesidade 8,0%; hipercolesterolemia 21,4%; hipertrigliceridemia 33,3% e dislipidemia 56,2%. O índice de massa corporal e os valores de colesterol total, glicemia, perímetro da cintura, índice cintura/quadril e pressão arterial sistólica e diastólica apresentaram correlação positiva e significativa com a idade. O grau de escolaridade mostrou correlação negativa com o perímetro da cintura, o índice cintura/quadril, a glicemia e a pressão arterial. Ao comparar com populações indígenas e não indígenas da Colômbia e de outros países, encontrou-se uma prevalência entre três e quatro vezes menor de diabetes mellitus; na população estudada há menos HTA ainda que existe tendência ao sobrepeso. Não se encontraram diferenças significativas em outros FR; todos eles foram mais frequentes em mulheres, em pessoas de escolaridade baixa e em indivíduos maiores. Os fatores que contribuem a estas diferenças são genéticos (homogeneidade étnica) e ambientais, como a maior atividade física dos homens, a dieta e a estrutura demográfica.
Subject(s)
Adult , Cardiovascular Diseases , Risk FactorsABSTRACT
Objetivos: Determinar las frecuencias alélicas y genotípicas del gen de la apolipoproteína E (APOE) en adultos de Medellín durante el año 2010. Métodos: Se tomó una muestra representativa de la población adulta de Medellín, mediante un muestreo polietápico estratificado por conglomerados. Se realizó genotipificación para APOE a cada uno de los sujetos participantes. En el análisis de frecuencias y asociación, se tuvo en cuenta el diseño muestral. Resultados: Las frecuencias de los alelos E2, E3 y E4 de APOE fueron del 3,9, el 92,0 y el 4,1% respectivamente. Las frecuencias genotípicas fueron: 2/2, el 0,2%; 2/3, el 6,8%; 2/4, el 0,6%; 3/3, el 85,0%; 3/4, el 7,2%, y 4/4, el 0,3%. Conclusiones: Las frecuencias alélicas y genotípicas de APOE en adultos de Medellín tienen una distribución similar a las reportadas en poblaciones suramericanas, y son datos que tienen valor para conocer el impacto poblacional de estas variantes genéticas en distintos trastornos psiquiátricos.
Objective: To determine the allelic and genotype frequencies of apolipoproteine E (APOE) gene in a representative sample of the adult population of Medellin in 2010. Methods: A representative sample of the adult population of Medellin, was obtained by means of a multi-stage, stratified, conglomerate based sampling method. APOE genotyping was carried out on each of the participants. The sampling design was taken into consideration for the frequencies and association analysis. Results: The frequencies of the APOE alleles E2, E3 and E4 were 3.9, 92.0 and 4.1%, respectively. The frequencies of the different APOE genotypes were as follows: 2/2, 0.2%; 2/3, 6.8%; 2/4, 0.6%; 3/3, 85.0%; 3/4, 7.2%, and 4/4, 0.3%. Conclusions: The allelic and genotype frequencies of APOE in an adult population of Medellin did not differ substantially from other series reported in South America. These data are important to determine the real impact of APOE on the population risk of several psychiatric diseases.
Subject(s)
Humans , Female , Middle Aged , Apolipoproteins E , Prevalence , Genotype , Apolipoproteins , Risk , Sampling Studies , Urban Area , Mental DisordersABSTRACT
El objetivo del estudio fue describir la calidad de vida relacionada con la salud (CVRS) y su asociación con aspectos sociodemográficos, el exceso de peso u obesidad y la actividad física (AF) en un grupo de adolescentes de la ciudad de Medellín (Colombia). Para evaluar dichas variables se aplicaron diferentes instrumentos a 399 participantes. Las dimensiones de la CVRS con mayores puntuaciones fueron Apoyo Social y Amigos y Estado de Ánimo y Sentimientos. Ser hombre, tener una menor edad, cursar primaria, tener padres con educación superior, pertenecer a estrato socioeconómico alto, no tener obesidad por porcentaje de grasa o perímetro abdominal y presentar un nivel alto de AF se relacionaron con una mejor CVRS.
The objective of the study was to describe health-related quality of life (HRQOL) and its association with socio-demographic aspects, overweight or obesity, and physical activity (PA) in a group of adolescents from the city of Medellín (Colombia). Different instruments were used in order to evaluate these variables in 399 participants. The HRQOL dimensions with the highest scores were Social Support and Friends and Mood and Feelings. Male primary school students with college-educated parents, belonging to a high socio-economic level, engaging in high levels of PA, and without obesity caused by fat percentage or abdominal perimeter proved to have a better HRQOL.
O objetivo do estudo foi descrever a qualidade de vida relacionada com a saúde (QVRS) e sua associação com aspectos sociodemográficos, o excesso de peso ou obesidade e a atividade física (AF) num grupo de adolescentes da cidade de Medellín (Colômbia). Para avaliar essas variáveis, aplicaram-se diferentes instrumentos a 399 participantes. As dimensões da QVRS com maiores pontuações foram Apoio Social e Amigos e Estado de Ânimo e Sentimentos. Ser homem, ter uma idade mais nova, cursar primário, ter pais com educação superior, pertencer a uma classe socioeconômica alta, não ter obesidade por porcentagem de gordura ou perímetro abdominal e apresentar um nível alto de AF se relacionaram com uma melhor QVRS.
ABSTRACT
Introducción: las intervenciones con ejercicio físico y orientación nutricional muestran cambios en el exceso de peso en jóvenes con el síndrome metabólico (SM); sin embargo, sus características y resultados son diversos.Objetivo: evaluar el efecto de una intervención con ejercicio físico y orientación nutricional sobre componentes del SM en jóvenes con exceso de peso.Materiales y métodos: estudio longitudinal con una evaluación antes y otra después, en nueve jóvenes entre 11 y 17 años. Se evaluaron aspectos antropométricos, frecuencia cardíaca en reposo (FCR), consumo pico de oxígeno (VO2pico), insulinemia, resistencia a la insulina (HOMA) y componentes de SM. La intervención consistió en 12 semanas de ejercicio supervisado, tres sesiones/semana de 90 minutos (aeróbico y de fuerza), más dos sesiones no supervisadas; el suministro semanal de frutas y verduras para cubrir las cinco porciones diarias recomendadas y educación nutricional individual y colectiva.Resultados: luego de la intervención disminuyeron la circunferencia de la cintura de 90,5 ± 11,0 a 88,1 ± 9,9 cm; el IMC de 30,2 ± 5,8 a 29,3 ± 5,6 kg/m2; la grasa corporal total de 39,8 ± 13,0 a 34,3 ± 9,0%; la glucemia de 86,0 ± 8,6 a 83,1 ± 5,0 mg/dL; la insulinemia de 23,2 ± 9,8 a 19,4 ± 7,6 µU/mL; el HOMA-IR de 2,89 ± 1,21 a 2,39 ± 0,93; la FCR de 87,9 ± 4,3 a 78,2 ± 5,5 bpm y aumentó el VO2pico de 36,3 ± 5,1 a 38,5 ± 4,1 mL/kg/min; de seis jóvenes con diagnóstico de SM al inicio, cuatro no lo presentaron al final.Conclusiones: participar en un programa de ejercicio y aumentar el consumo de frutas y verduras en los jóvenes con exceso de peso y componentes del SM generó modificaciones positivas en la composición corporal, el VO2pico, la FCR y la glucemia así como en los componentes y prevalencia del SM.
Introduction: Interventions with physical exercise and nutritional guidance show changes in overweight among young people suffering from the metabolic syndrome (MS); nevertheless, their characteristics and results vary.Objective: To assess the effect of an intervention with physical exercise and nutritional guidance on components of the MS among overweighted young people.Materials and methods: Longitudinal study with an assessment before and another after the intervention in nine young people aged 11 to 17 years. Anthropometric aspects, resting heart rate, peak oxygen consumption (VO2peak), insulinemia, HOMA, and components of the MS were assessed. Intervention consisted of 12 weeks of supervised exercise, three 90-minute sessions/week (aerobic and strength), plus two unsupervised sessions; the weekly supply of fruits and vegetables in order to cover the five recommended daily servings, and individual and group nutrition education.Results: With the intervention waist circumference decreased from 90.5 ± 11.0 to 88.1 ± 9.9 cm; BMI from 30.2 ± 5.8 to 29.3 ± 5.6 kg/m2; total body fat from 39.8 ± 13.0 to 34.3 ± 9.0%; glycemia from 86.0 ± 8.6 to 83.1 ± 5.0 mg/dL; insulinemia from 23.2 ± 9.8 to 19.4 ± 7.6 µU/mL; HOMA-IR from 2.89 ± 1.21 to 2.39 ± 0.93; resting heart rate from 87.9 ± 4.3 to 78.2 ± 5.5 rpm, and VO2peak increased from 36.3 ± 5.1 to 38.5 ± 4.1 mL/kg/min. Four out of six young people with the diagnosis of MS at the beginning of the study did not present it at the end.Conclusions: Participating in an exercise program and increase in the consumption of fruits and vegetables among overweighted young people with components of the MS produced positive modifications in body composition, VO2peak, resting heart rate, and glycemia, as well as in the components and prevalence of the MS.
Subject(s)
Humans , Adolescent , Food and Nutrition Education , Exercise , Overweight , Metabolic SyndromeABSTRACT
Introduction. Polymorphisms in promoters of genes code for cytokines that affect transcription levels. Several have been associated with leprosy patients that have functional and clinical implications. Objective. Polymorphisms in the promoter of the IL10 gene of leprosy patients will be compared frequencies in normal population. Materials and methods. SNPs (single nucleotide polymorphism) -1082 A/G (rs1800896), -819C/T (rs1800871), and -592A/C (rs1800872) were identified in 100 leprosy patients and in a control group of 100 volunteers from a leprosy endemic region of Colombia. Results. The genotypes C/C and C/T in the SNP -819 were associated together with leprosy (OR=4.34, p<0.001).Similarly, the genotypes C/C and C/A in the -592 SNP showed an association (OR=4.3, p<0.001). The haplotypes -819C-519C and -1082A-819C-592C showed significant association (OR=4.34, p<0.001 and OR=6.25, p<0.001) respectively. These haplotypes in homozygosis conditions were also associated with leprosy: -819C-519C/-819C-519C (OR=4.34, p<0.001), -1082A -819C-592C/-1082A -819C-592C (OR=1.90, p=0.04). The SNP -1082 was not associated with leprosy in this population. Conclusions. The haplotypes associated with leprosy, -1082A-819C-592C/-1082A-819C-592C, have been reported as low producers of IL-10. Functionally, the low production of IL-10 may have immune response consequences and clinical implications. Additional haplotypes of IL-10 have been reported as markers for leprosy susceptibility or resistance in other ethnic populations. This suggests that differences in distribution of diverse IL-10 gene polymorphisms among ethnic groups may indicate important gene-disease associations.
Introducción. Se han reportado polimorfismos en los genes promotores que codifican para citocinas y que afectan los niveles de transcripción, con implicaciones clínicas y funcionales en pacientes con lepra. Objetivo. Detectar los polimorfismos en el gen promotor de la interleucina 10 (IL-10), de los polimorfismos de un solo nucleótido (Single Nucleotide Polymorphisms, SNP) -1082 A/G (rs1800896), -819C/T (rs1800871) y -592A/C (rs1800872), en 100 pacientes con lepra y un grupo control de 100 voluntarios, de una región endémica de Colombia. Resultados. Los haplotipos -819C-519C y -1082A-819C-592C mostraron asociación significativa con lepra: OR=4,34, p=1 x 10-3, y OR=6,25, p=5 x 10-4, respectivamente. Estos haplotipos en condiciones de homocigoto, están también asociados con lepra: -819C-519C/-819C-519C (OR=4,34 p=1 x 10-3), -1082A -819C-592C/-1082A -819C-592C (OR=1,90 y p=0,04). El SNP -1082 no se encontró asociado con lepra en esta población. Los genotipos C/C y C/T en el SNP -819, se encontraron asociados a lepra (OR=4,34, p=1 x 10-3); de igual manera, los genotipos C/C y C/A en el SNP -592 mostraron asociación (OR=4,34, p=1 x 10-3). Conclusiones. El haplotipo que encontramos asociado con lepra, -1082A-819C-592C/-1082A-819C-592C, se ha relacionado con baja producción de IL-10. Funcionalmente, esta baja producción de IL-10 puede tener consecuencias en la respuesta inmunitaria, además de implicaciones clínicas. Se han reportado diferentes haplotipos de IL-10 como marcadores de vulnerabilidad y resistencia de lepra en otras poblaciones, lo cual sugiere que las diferencias en la distribución de diversos polimorfismos del gen de IL-10 entre grupos étnicos, es un factor importante al determinar la asociación entre enfermedad y genes.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Young Adult , /genetics , Leprosy/genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic/genetics , Case-Control Studies , Colombia/epidemiology , Endemic Diseases , Ethnicity/genetics , White People/genetics , Gene Frequency , Genetic Predisposition to Disease , Genotype , Haplotypes , /biosynthesis , /physiology , Leprosy/epidemiology , Leprosy/microbiology , Mycobacterium leprae/isolation & purificationABSTRACT
El desconocimiento de la lepra es común en la población general al igual que entre los médicos y el personal de la salud. Se cree que esta enfermedad ya no existe; tal vez su imagen bíblica y milenaria refuerce la idea de su eliminación. Sin embargo, la lepra continúa siendo un problema de salud pública en varios países; entre los más afectados están India y Brasil. Después del inicio de la poliquimioterapia (PQT) en la novena década del siglo XX la prevalencia de la lepra disminuyó considerablemente pero no ocurrió lo mismo con la incidencia, lo que se atribuye al poco impacto de dicho tratamiento sobre el control de la transmisión y a la existencia de un reservorio aún no identificado con exactitud. Los convivientes de los leprosos tienen alto riesgo de sufrir la enfermedad en cualquier momento de la vida, pero hasta ahora no se ha podido determinar cuáles convivientes infectados desarrollarán la enfermedad. En Colombia se informan de 400 a 550 casos de lepra cada año, lo cual sugiere que la transmisión del Mycobacterium leprae continúa a pesar de que el país está considerado en la fase de poseliminación. Este artículo presenta una revisión histórica de la lepra desde los primeros informes disponibles hasta los avances moleculares más recientes. Incluye cómo ha evolucionado la comprensión de la enfermedad, su caracterización clínica, las medidas de control y saneamiento, el tratamiento y la epidemiología.
Ignorance about leprosy is common both in the general population and among physicians and health personnel. It is believed that this disease no longer exists. Perhaps its image as a biblic and ancient scourge reinforces the idea of its elimination. However, leprosy continues to be a public health problem in several countries; among the most affected are India and Brazil. After multidrug therapy (MDT) started during the ninth decade of the XX century prevalence of leprosy dramatically decreased. Incidence, however, did not follow the same trend, probably because of the low impact of MDT on transmission, and the existence of an as yet unidentified reservoir. Familial contacts of leprosy patients are at high risk of suffering the disease at any moment in their lives. So far it has not been possible to determine which ones of the infected contacts will develop the disease. Between 400 and 550 cases of leprosy are reported every year in Colombia. This fact suggests that transmission of Mycobacterium leprae still occurs despite the country being classified as in the postelimination phase. This article presents a historical review on leprosy from the earliest available reports to the more recent advances in the molecular understanding of the disease and its agent. It includes how the comprehension about it has evolved, its clinical characterization, public health control measures, therapy and epidemiology.
Subject(s)
Humans , Elephantiasis/history , Skin Diseases, Bacterial , Leprosy , Leprosy, Multibacillary , Leprosy, Paucibacillary , Leprosy/history , Mycobacterium leprae , Public Health , Brazil , Colombia , IndiaABSTRACT
Introducción: mutaciones en mtDNA causan citopatias mitocondriales, la más común de ellases el síndrome MELAS; la transición A3243G en tRNA de leucina (tRNALeu) se presenta en 80% depacientes. La heteroplasmia, observada en citopatias mitocondriales, consiste en coexistenciade moléculas mutadas y normales en una célula, situación en la cual, dependiendo de su cantidad,afecta su función con expresión clínica variable.Objetivo: evaluar el comportamiento de la cantidad de heteroplasmia de la mutación 3243G ensu expresión clínica y en la dependencia de variantes nucleares.Pacientes y métodos: se buscaron mutaciones en el gen que codifica para el tRNA de leucinapor secuencia y por PCR-RFLP en 34 pacientes, y se tamizó en familiares de los portadores de lamutación. Se tipificaron cuatro Specific Population Allele (SPA) en pacientes y familiares con lamutación A3243G.Resultados: se halló la mutación A3243G en el tRNALeu en dos pacientes, luego de tamizar lamutación A3243G en ambas familias se evaluó la cantidad de mtDNA mutado (MDNA),encontrando que los casos índices de ambas familias presentaron la mayor cantidad de MDNA;en la primera familia se detectó la mutación en 15 miembros que presentaron diversos síntomas.En la segunda familia se detectó la mutación en un miembro con parálisis cerebral, en dos conmigraña y en uno asintomático.Conclusiones: la severidad de los síntomas se correlaciona con la cantidad de MDNA, se encontróademás correlación entre mtDNA mutado (MDNA) y el Índice de Ancestría Amerindio en cadaindividuo (IAA), indicando una posible influencia del contexto nuclear amerindio en lasegregación y replicación mitocondrial.
Mitochondrial DNA mutations cause mitochondrialcytopathies. Among them Mitochondrial Encephalomyopathy,Lactic Acidosis, and Stroke-like episodes(MELA) is the commonest. The transition 3243A>G inthe Leucine tRNA is present in 80% of the patients.Heteroplasmy is observed in mitochondrialcytopathies, characterized by the coexistence of mutantand wild type molecules in a cell. Depending on thelevel of heteroplasmy, function and clinicalmanifestations might result affected.Objective: To test the degree of heteroplasmy of themutation 3243G on its expression (syntoms) andnuclear-variants dependence.Patients and methods: Mutations in the tRNALeu genewere sought in 34 patients by sequencing and PCR-RFLP.Four SPA (specific population alleles) were typed inpatients and their relatives carrying the mutation3243A>G.Results: The mutation 3243A>G in the Leucine tRNAgene was found in two patients. This mutation wasscreened in their relatives and the amount of mutantDNA (MDNA) was assessed. The index cases presentedwith the higher amounts of MDNA in both families. Infamily one, the mutation was detected in 14members, three of which presented with short stature,one with hearing loss, one with type 2 diabetes, 8 withmigraine and one healthy individual. In family two themutation was detected in one member with brainparalysis, two with migraine and one healthyindividual.Conclusions: Severity of the symptoms in patientsaffected with MELAS is correlated with the amount ofMDNA. Furthermore, it was found a correlationbetween MDNA and IAA, suggesting a possible effect ofamerind nuclear ontext in The mitochondrialsegregation and replication.
Subject(s)
Humans , Mutation/genetics , MELAS Syndrome/geneticsABSTRACT
Hemos encontrado ligamiento y asociación de la diabetes mellitus tipo 1 (T1D) con 2p25. En esta región se halla el gen TPO. Nuestro objetivo fue estudias la asociación de dicho gen con la susceptibilidad a la T1D en un grupo de familias colombianas, todas ellas originarias de Antioquia, una población especial en el noroccidente del país. Se analizaron cien tríos familiares con T1D. Estas familias ya habían sido estudiadas para anticuerpos contra la ácido-glutámico-descarboxilasa (GAD) y el locus marcador D2S319. Para una caracterización adicional se estudió a los probandos para autoanticuerpos contra insulina, tiroperoxidasa (TPO) y fosfatasa de tirosina 2 (IA2). Se estudiaron en TPO dos polimorfismos de un solo nucleótido (SNP): rs4927611 y rs732609. Se escogieron estos marcadores teniendo en cuenta que el polimorfismo cambia el aminoácido codificado y una frecuencia del alelo menor, MFA, ≥ 0,3. La tipificación de los SNP se llevó a cabo mediante la reacción en cadena de la polimerasa-restricción de fragmentos de longitud polimórfica (PCR-RFLP) y el tetraprimer amplification refractory modification system (ARMS-PCR). Los análisis de equilibrio de Hardy-Weinberg (HWE) y de desequilibrio de ligamiento (LD) se hicieron separadamente tanto en los padres como en los probandos. Se estudió la asociación genética por medio de la prueba de desequilibrio de la transmisión (TDT). Encontramos que 86% de los pacientes presentaban al menos uno de los tres autoanticuerpos estudiados. Tanto los probandos como sus padres se encontraron en equilibrio de Hardy-Weinberg para ambos SNP. Además, los dos marcadores se encontraron en estrecho desequilibrio de ligamiento (LD) (p < 0,0001). Se identificó un haplotipo asociado con susceptibilidad a la enfermedad (p = 0,0116). Se halló autoinmunidad en una proporción similar a la previamente informada. Se encontró que un haplotipo en el gen TPO está asociado con la enfermedad. Tal haplotipo se caracteriza por los alelos G y A en los SNP rs4927611 y rs732609, respectivamente. Nuestros resultados sugieren una posible participación causal del gen TPO en la T1D. Para verificarlos, se está recolectando una muestra de similar tamaño en la misma población colombiana.
We have found linkage and association of type 1 diabetes (T1D) to 2p25. The TPO gene lies within this region. Our aim was to test the association of this gene with the susceptibility to T1D in a group of Colombian families, all of them originated in Antioquia, a special population in northwestern Colombia. One hundred familial trios with type 1 diabetes (T1D) were analyzed. They had already been studied for anti-glutamic acid descarboxilase (GAD) antibodies and the marker locus D2S319. For further characterization, the probands were tested for autoantibodies against insulin, TPO and thyrosine phosphatase 2 (IA-2). Two single nucleotide polymorphisms (SNPs) (rs4927611 and rs732609) were tested in TPO. These two markers were chosen considering that the polymorphism changes the encoded amino-acid and a minor allele frequency, MAF, ≥ 0.3. SNP typing was carried out by means of the polymerase chain reaction/restriction fragment length polymorphisms (PCR-RFLP)and the tetraprimer amplification refractory mutation system (ARMS-PCR) methods. Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD) analyses were separately tested on both parents and probands. Genetic association was tested by the transmission disequilibrium test (TDT). It was found that 86% of the patients presented at least one of the three auto-antibodies tested. Bothparents and probands were found in HWE for both SNPs. In addition, the two markers were found in tight LD (p < 0.0001). A haplotype associated with susceptibility to the disease was identified (p = 0.0116). Autoimmunity was found in a proportion similar to that previously reported. It was found that a haplotype at TPO gene is associated with the disease. Such haplotype is characterized by alleles G and A at rs4927611 and rs732609 SNPs, respectively. Our results suggest a possible causative participation of the TPO gene in T1D. In order to verify them, a sample of equivalent size is currently being collected, from the same population in Colombia.
Subject(s)
Humans , Diabetes Mellitus/genetics , Genetics/statistics & numerical dataABSTRACT
Introducción: El cáncer colorrectal (CCR) es una de las entidades malignas más frecuentes en nuestro medio y ocupa el cuarto lugar después del cáncer de cérvix, seno y estómago; esta enfermedad continúa siendo diagnosticada en la mayoría de los casos en estadios avanzados. En Antioquia, la incidencia en menores de 40 años es de 20,9 por ciento, siendo esta tasa la más alta y el doble de lo informado a escala mundial para este grupo de edad. Propósito: Caracterización molecular del polimorfismo 399 C>T en el exón 3 del gen MSH2 en pacientes con cáncer colorrectal hereditario (HNPCC) y esporádico.Pacientes y métodos: Se analizaron seis pacientes con cáncer colorrectal hereditario no polipoideo (CCHNP), seis con cáncer colorrectal esporádico y seis individuos sanos. La extracción del DNA se realizó a partir de sangre periférica. Las muestras se amplificaron por PCR; el polimorfismo se detectó por secuenciamiento directo.Resultados: En todos los individuos estudiados con cáncer colorrectal hereditario y esporádico, así como en los individuos sanos se detectó el polimorfismo 399 C>T en el exón 3 del gen MSH2.Conclusiones: El cambio molecular detectado no varía el aminoácido que se codifica, por lo que se considera como una mutación neutra no identificada previamente en otras poblaciones. Varios polimorfismos se han asociado con la susceptibilidad para desarrollar cáncer colorrectal. Por lo tanto, futuros estudios son necesarios para determinar si este polimorfismo está relacionado con el desarrollo del cáncer colorrectal en la población colombiana
Subject(s)
Humans , Colorectal Neoplasms, Hereditary Nonpolyposis , Polymorphism, Genetic , Rectal NeoplasmsABSTRACT
LA enfermedad de Alzheimer es un problema mundial de salud pública. El estudio de los mecanismos moleculares responsables de su aparición permitirá avances terapéuticos y en las técnicas para la evaluación de las personas afectadas y de las que están en riesgo de desarrollar la enfermedad. La mutación E280A en el gen de la Presenilina 1 (PS1) es responsable de una forma grave de la enfermedad de Alzheimer familiar. Con el fin de conocer su efecto sobre la Proteína Precursora de Amiloide (PPA), se cuantificó la producción de esta por células de sangre periférica (mononucleares y linfocitos B) de individuos portadores de dicha mutación. Se analizaron cultivos celulares (HeLa y CHO) como controles positivos, y sangre periférica procedente de portadores sanos de la mutación, de portadores afectados y de un grupo control sano, no portador. Todas las células (HeLa, CHO, mononucleares y linfocitos B) se analizaron por citometría de flujo para detectar la PPA en la membrana citoplasmática y en el espacio intracelular. Se halló un nivel mayor de expresión de esta proteína en el interior de las células que en la membrana celular. En células HeLa y CHO los niveles de expresión intracelular fueron muy variables mientras que en los mononucleares fueron uniformemente bajos. Otros trabajos han detectado niveles mayores de la proteína en los enfermos, pero nuestros resultados indican que no hay diferencia entre los controles sanos, los portadores sanos y los portadores enfermos, lo cual indica que la mutación E280A de la PS1 no ejerce un papel directo en la expresión de la PPA en células mononucleares de sangre periférica. AUT
Abstract Alzheimer's disease is a public health problem both in Colombia and worldwide. Study of the molecular mechanisms involved in this disease may allow the development of methods for evaluation and treatment of Alzheimer's disease patients and people at risk. Mutation E280A in the presenilin-1 gene leads to the development of an aggressive form of familial Alzheimer's disease. In order to define the role of such mutation on the expression of Amyloid Precursor Protein in peripheral blood mononuclear cells and B lymphocytes we carried out a study in three groups of people, namely: healthy carriers of the mutation, affected carriers and healthy non-carriers as controls. Flow cytometry was used for the detection of Amyloid Presursor Protein in cell membranes and intracellulary; HeLa and CHO cells were used as positive controls. Expression level of Amyloid Precursor Protein was higher in the intracellular compartment than in the cell membrane. The levels of expression in the intracellular compartment of HeLa and CHO cells were variable in contrast with those of peripheral blood mononuclear cells in which they were lower but stable. Contrariwise to the results of other authors, who have detected higher levels of Amyloid Precursor Protein in Alzheimer's disease patients, our results revealed no difference between healthy controls and carriers of the E280A mutation in the presenilin-1 gene, either diseased or healthy. Our results show that this mutation does not directly change the expression of Amyloid Precursor Protein in peripheral blood mononuclear cells
Subject(s)
Amyloid beta-Protein Precursor , Alzheimer Disease , Flow CytometryABSTRACT
El objetivo de este estudio es caracterizar clínicamente a los pacientes con trastorno afectivo bipolar I (TAB I), teniendo en cuenta la presencia de agregación familiar. Métodos: éste es un estudio observacional de corte transversal. Se extendieron genealogías de pacientes con TAB I, se identificaron familiares posibles afectados y psiquiatras que desconocían los antecedentes familiares de los sujetos realizaron una entrevista diagnóstica para estudios genéticos (DIOS) para confirmar el diagnóstico y recolectar información clínica. Se efectuó el análisis estadístico con el método de correspondencias múltiples. Resultados: se describen las características clínicas del TAB I en este grupo de pacientes. En el análisis de correspondencias se identificaron diversas agrupaciones sintomáticas. Se encontró asociación entre agregación familiar y mayor gravedad de los episodios depresivos junto con peor funcionamiento intercrítico. Conclusiones: (1) las características clínicas y agrupaciones sintomáticas encontradas son similares a las descritas en la literatura médica. (2) Los pacientes con agregación familiar parecen presentar un trastorno de mayor gravedad. (3) El análisis de correspondencias múltiples es una herramienta útil para estudios sobre fenomenología psiquiátrica