Polymorphisms of leptin-melanocortin system genes associated with obesity in an adult population from Barranquilla / [Polimorfismos de los genes del sistema leptina-melanocortina asociados con la obesidad en la población adulta de Barranquilla].

Introduction: Obesity is considered a serious public health problem. Efforts have been directed to search for candidate genes such as LEP, LEPR, and MC4R involved in the leptin-melanocortin system. The neuroendocrine regulation of these genes on energy intake and balance influences the pathogenesis of this disease. Contradictory results regarding the association of these genes with obesity raise the need for new research. Objective: To analyze the association between obesity and LEP rs2167270, LEPR rs1137101, and MC4R rs17782313 polymorphisms and the clinical and biochemical variables in obese adults from Barranquilla, Colombia. Materials and methods: We analyzed 111 obese adults and 155 non-obese individuals as controls. The polymorphisms were determined by real-time PCR. Besides, anthropometric measures, blood pressure, and biochemical tests were evaluated. Results: No statistical differences were found in allele and genotype frequencies of gene polymorphisms between groups. The CC genotype of MC4R rs17782313 polymorphism was associated with increased systolic blood pressure and T allele and TT genotype, with decreased HDL cholesterol in obese adults. The effect of the other polymorphisms on these variables was not evidenced. Conclusions: LEP rs2167270, LEPR rs1137101, and MC4R rs17782313 polymorphisms were not associated with obesity in the population under study. MC4R rs17782313 polymorphisms were associated with an increase in systolic blood pressure and a decrease in HDL cholesterol.

Introducción. La obesidad se considera un grave problema de salud pública y por ello se hacen esfuerzos en la búsqueda de genes como el LEP, el LEPR y el MC4R del sistema leptina-melanocortina, el cual opera en la regulación neuroendocrina de la ingestión y el equilibrio energético e influye en la patogenia de la enfermedad. Los resultados contradictorios en torno a la asociación de estos genes con la obesidad plantean la necesidad de nuevas investigaciones. Objetivo. Analizar los polimorfismos rs2167270 del gen LEP, rs1137101 del gen LEPR y rs17782313 del gen MC4R asociados con la obesidad y sus variables clínicas y bioquímicas en una muestra de pacientes adultos de Barranquilla. Materiales y métodos. Se estudiaron 111 personas obesas y 155 no obesas como controles. Los polimorfismos se determinaron mediante reacción en cadena de la polimerasa (PCR) en tiempo real. Se tomaron las medidas antropométricas, se evaluó la presión arterial y se hicieron pruebas bioquímicas. Resultados. No se encontraron diferencias estadísticas en la frecuencia alélica y genotípica de los polimorfismos en los grupos estudiados. En cuanto a las variables clínicas y bioquímicas, el genotipo CC del polimorfismo rs17782313 del gen MC4R, se asoció con un aumento de la presión arterial sistólica y, el alelo T y su genotipo homocigoto, con una disminución del colesterol HDL en los obesos. No se evidenció ningún efecto de los otros polimorfismos en estas variables. Conclusiones. Los polimorfismos rs2167270 del gen LEP, rs1137101 del gen LEPR y rs17782313 del gen MC4R, no se asociaron con obesidad en la población analizada. Se encontró que el polimorfismo rs17782313 del gen MC4R influyó en el aumento de la presión arterial sistólica y la disminución del colesterol HDL en las personas obesas.

APOE gene polymorphism analysis in Barranquilla, Colombia.

INTRODUCTION: The genetic variability present in the APOE gene polymorphism is considered an important factor associated with predisposition to diseases affecting lipid metabolism, as well as heart diseases and Alzheimer's disease, among others. Understanding it as a risk factor in different populations and ethnic groups is a useful tool.  OBJECTIVE: To analyze the APOE gene polymorphism and determine allelic and genotypic frequencies of a representative sample of population from Barranquilla, Colombia.  MATERIALS AND METHODS: We performed a descriptive and comparative study. The sample size was 227 unrelated individuals from Barranquilla, Colombia.  RESULTS: The most frequent allele was the ε3, with 85%, followed by the ε4 allele (13%) and ε2 (1.8%). The genotypes found were: ε3/ε3: 71.8%, ε3/ε4: 24.2%, ε2/ε3: 2.2%, ε2/ε4: 1.3% and ε4/ε4: 0.4%. The ε2/ε2 genotype was not found in this study. The sample exhibited the Hardy-Weinberg equilibrium.  CONCLUSION: The frequency of the ε3 allele and the ε3/ε3 genotype was similar to that reported in the literature in countries like Brazil, Mexico, Colombia, and in some Colombian Amerindian ethnic groups. The ε2/ε2 genotype was absent. This result is consistent with those found in other population groups worldwide. The frequency of the ε4 allele and the genotypes associated in this population could be related to the presence of diseases such as hypercholesterolemia, myocardial infarction and Alzheimer.

Análisis del polimorfismo del gen APOE en la población de Barranquilla, Colombia / APOE gene polymorphism analysis in Barranquilla, Colombia

Introducción. La variabilidad genética del polimorfismo del gen APOE se considera un importante factor asociado a la predisposición a las enfermedades que afectan el metabolismo lipídico, a las enfermedades coronarias y a la enfermedad de Alzheimer, entre otras. En este sentido, es útil conocer este factor de riesgo en diferentes poblaciones y grupos étnicos. Objetivos. Analizar el polimorfismo del gen APOE y determinar las frecuencias alélicas y genotípicas de una muestra representativa de la población de Barranquilla, Colombia. Materiales y métodos. Se hizo en Barranquilla un estudio descriptivo y comparativo de 227 individuos no relacionados. Resultados. El alelo e3 se presentó con mayor frecuencia (85 %), seguido del alelo e4 (13 %) y, con menor frecuencia, el alelo e2 (1,8 %). Los genotipos observados fueron los siguientes: e3/e3 en 71,8 %, e3/e4 en 24,2 %, e2/e3 en 2,2 %, e2/e4 en 1,3 % y e4/e4 en 0,4 %. El genotipo e2/e2 no se encontró en este estudio. La muestra representativa de la población estaba en equilibrio de Hardy-Weinberg. Conclusiones. Las frecuencias alélicas e3 y el genotipo e3/e3 encontrados en la población estudiada, fueron similares a lo informado por la literatura científica en países como Brasil, México y Colombia, y en algunos grupos étnicos amerindios colombianos. No se encontró el genotipo e2/e2, resultado que coincide con otras poblaciones estudiadas a nivel mundial. La frecuencia del alelo e4 y sus genotipos asociados en esta población, podría estar relacionada con la presencia de enfermedades como la hipercolesterolemia, el infarto de miocardio y la enfermedad de Alzheimer.

Introduction: The genetic variability present in the APOE gene polymorphism is considered an important factor associated with predisposition to diseases affecting lipid metabolism , as well as heart diseases and Alzheimer´s disease, among others. Understanding it as a risk factor in different populations and ethnic groups is a useful tool. Objective: To analyze the APOE gene polymorphism and determine allelic and genotypic frequencies of a representative sample of population from Barranquilla, Colombia. Materials and methods: We performed a descriptive and comparative study. The sample size was 227 unrelated individuals from Barranquilla, Colombia Results: The most frequent allele was the e 3, with 85%, followed by the e 4 allele (13%) and e 2 (1.8%). The genotypes found were: e 3/ e 3: 71.8%, e 3/ e 4: 24.2%, e 2/ e 3: 2.2%, e 2/ e 4: 1.3% and e 4/ e 4: 0.4%. The e 2/ e 2 genotype was not found in this study. The sample exhibited the Hardy-Weinberg equilibrium. Conclusion : The frequency of the e 3 allele and the e 3/ e 3 genotype was similar to that reported in the literature in countries like Brazil, Mexico, Colombia, and in some Colombian Amerindian ethnic groups. The e 2/ e 2 genotype was absent. This result is consistent with those found in other population groups worldwide. The frequency of the e 4 allele and the genotypes associated in this population could be related to the presence of diseases such as hypercholesterolemia, myocardial infarction and Alzheimer.

NAT2 gene polymorphisms in three indigenous groups in the Colombian Caribbean Coast region.

OBJECTIVE: To study the NAT2 gene polymorphisms 481T, 590A and 857A in the Chimila, Wiwa and Wayuu indigenous groups of the Colombian Caribbean to determine the frequencies of the alleles NAT2*4, NAT2*5, NAT2*6, and NAT2*7 and to determine the types of acetylators present in these populations. METHODS: A total of 202 subjects were studied: 47 Chimila, 55 Wiwa, and 100 Wayuu. The polymorphisms were identified using a real-time PCR method for allelic discrimination designed using Taqman of Applied Biosystems. RESULTS: The following alleles were found at the highest frequency in the following groups: the NAT2*4 allele (wild type) in the Wayuu group (55.3%), the NAT2*5 allele in the Wiwa group (34.5%), and the NAT2*7 allele in the Chimila group (24.2%). A higher frequency of the rapid acetylator status was found in the Wayuu group (31.3%) and Chimila group (29.5%) compared with the Wiwa group (12.7%). The intermediate acetylator status distribution was very similar in all three groups, and the frequency of the slow acetylator status was higher in the Wiwa group (32.7%) compared with the Chimila and Wayuu groups (20.5% and 21.2%, respectively). CONCLUSION: The results demonstrated the allelic distribution and pharmacogenetic differences of the three groups studied and revealed the most frequent acetylator status and phenotype. Because of the high prevalence of slow acetylators, a greater incidence of tuberculosis (TB) drug-induced hepatotoxicity is predicted in these populations, with a higher frequency in the Wiwa group.

OBJETIVO: Estudiar los polimorfismos tipo SNP (del inglés-single nucleotide polymorphism) 481T, 590A y 857A del gen NAT2, en los grupos indígenas Chimila, Wiwa y Wayúu del Caribe Colombiano para determinar las frecuencias de los alelos NAT2*4, NAT2*5, NAT2*6 y NAT2*7 y caracterizar el tipo de acetiladores presentes en estas poblaciones. MÉTODOS: Se estudiaron 202 individuos en total, 47 Chimila, 55 Wiwa y 100 Wayúu. Los polimorfismos se determinaron mediante la técnica de PCR en tiempo real por el método de discriminación alélica Taqman de Applied Biosystems. RESULTADOS: El alelo NAT2*4 (wild type) mostró una mayor frecuencia en el grupo Wayúu (55.3%), el alelo NAT2*5 en el grupo Wiwa (34.5%) y el alelo NAT2*7 en el grupo Chimila (24.2%). Se encontró una mayor frecuencia del estado acetilador rápido en el grupo Wayúu (31.3%) y en el grupo Chimila (29.5%) al compararse con el grupo Wiwa (12.7%). La distribución del estado acetilador intermedio es muy similar en los tres grupos, y para el estado acetilador lento observamos que en el grupo Wiwa la frecuencia es mayor (32.7%) con respecto a Chimila y Wayúu con 20.5% y 21.2% respectivamente. CONCLUSIONES: Los resultados permitieron conocer la distribución alélica y el componente farmacogenético de los tres grupos estudiados; igualmente, deducir el estado acetilador y/o fenotipo más frecuente. Debido a la alta prevalencia de acetiladores lentos, se podría predecir un aumento de la incidencia de hepatotóxicidad inducida por medicamentos antituberculosos como la Isoniacida indicados en estas poblaciones y en mayor frecuencia en el grupo Wiwa.

Insuficiencia cardíaca en la enfermedad renal crónica avanzada: relación con el acceso vascular / Congestive heart failure in patients with advanced chronic kidney disease: association with pre-emptive vascular access placement

Introducción: La insuficiencia cardíaca congestiva (ICC) es una complicación frecuente en la enfermedad renal crónica (ERC). Además de los factores de riesgo clásicos, otros relacionados más específicamente con la ERC, como la anemia, la sobrehidratación o los accesos vasculares, también podrían jugar un papel importante. Objetivos: Determinar la incidencia y las características clínicas asociadas al desarrollo de ICC en pacientes con ERC avanzada y analizar la influencia de la creación de accesos vasculares prediálisis sobre esta complicación. Pacientes y métodos: Estudio de cohorte prospectivo y de observación en el que se incluyeron 562 pacientes (edad media 65 ± 15 años, 260 mujeres) con un filtrado glomerular medio de 15,1 ± 5,0 ml/min, no en diálisis. La variable de resultado principal fue el desarrollo de al menos un episodio de ICC definida por criterios clínicos y radiológicos convencionales. Además de los datos demográficos y clínicos de interés, se incluyó también como covariable la fístula arteriovenosa (FAV). Resultados: Con una mediana de seguimiento de 461 días, la incidencia de ICC fue de 19 episodios por cada 1000 pacientes/año, presentando esta complicación un 17% del total de los pacientes. Mediante regresión logística multivariable, los mejores determinantes del desarrollo de ICC fueron, además de los factores de riesgo clásicos (mujer, añosa, obesa, diabética, con antecedentes de cardiopatía), la realización con éxito de una FAV (odds ratio: 9,541; intervalo de confianza 95%: 4,841; 18,806; p < 0,0001). Mientras que 4 de los 51 pacientes (8%) con FAV distales desarrollaron ICC, 43 de los 109 pacientes (40%) con FAV proximales desarrollaron esta complicación. No se observaron diferencias en la mortalidad de los pacientes con o sin ICC, aunque el inicio no programado (urgente) de diálisis fue mucho más frecuente entre los que desarrollaron ICC que en el resto (63 vs. 3%, p < 0,0001). Conclusiones: La incidencia de ICC es muy elevada en pacientes con ERC avanzada prediálisis. Además de los factores de riesgo clásicos, la realización de un acceso vascular incrementa significativamente la probabilidad de desarrollo de esta complicación cardiovascular (AU)

Introduction: Congestive heart failure (CHF) is a common complication in patients with chronic kidney disease (CKD). In addition to classical risk factors (e.g. age and pre-existing cardiac diseases), other potential reversible abnormalities linked to CKD such as anaemia, volume overload, or vascular access placement may also influence the incidence and severity of acute exacerbations of CHF. Objective: This study aims to determine the incidence and main determinants of CHF in a cohort of patients with stage 4-5 pre-dialysis CKD. Patients and Method: The study group consisted of 562 patients (mean age: 65±15 years, 260 females, 31% diabetics). Native arteriovenous fistulas (AVF) were created in 160 patients who chose haemodialysis as the initial technique for renal replacement therapy. The main outcome variables were: acute decompensated CHF (defined by standard criteria), dialysis initiation (planned and unplanned), and death before dialysis initiation. In addition to demographics, comorbidities, and clinical and biochemical data, AVF creation was also included as a potential determinant of CHF in multiple logistic regression models. Results: Ninety-five patients (17%) developed at least one episode of acute decompensated CHF, and the incidence rate was 19 episodes per 1000 patient-years. In addition to classical risk factors (age, female sex, obesity, diabetes, and previous history of CHF or coronary artery disease), creation of a successful AVF significantly increased the risk of CHF (OR=9.54, 95% CI: 4.84-18.81, P<.0001). In 47 out of 95 patients who developed CHF, a functioning AVF had previously been created, 92% of which were upper arm native AVF, with a median of 51 days between the surgical procedure and CHF episode. The mortality of patients with CHF was similar to that of the rest of the study patients, although unplanned dialysis initiation was significantly more frequent in those who developed CHF. Conclusions: Acute decompensated CHF episodes are common in pre-dialysis CKD patients. In addition to classical risk factors, pre-emptive AVF placement was strongly associated with the development of CHF (AU)

Congestive heart failure in patients with advanced chronic kidney disease: association with pre-emptive vascular access placement.

INTRODUCTION: Congestive heart failure (CHF) is a common complication in patients with chronic kidney disease (CKD). In addition to classical risk factors (e.g. age and pre-existing cardiac diseases), other potential reversible abnormalities linked to CKD such as anaemia, volume overload, or vascular access placement may also influence the incidence and severity of acute exacerbations of CHF. OBJECTIVE: This study aims to determine the incidence and main determinants of CHF in a cohort of patients with stage 4-5 pre-dialysis CKD. PATIENTS AND METHOD: The study group consisted of 562 patients (mean age: 65 +/- 15 years, 260 females, 31% diabetics). Native arteriovenous fistulas (AVF) were created in 160 patients who chose haemodialysis as the initial technique for renal replacement therapy. The main outcome variables were: acute decompensated CHF (defined by standard criteria), dialysis initiation (planned and unplanned), and death before dialysis initiation. In addition to demographics, comorbidities, and clinical and biochemical data, AVF creation was also included as a potential determinant of CHF in multiple logistic regression models. RESULTS: Ninety-five patients (17%) developed at least one episode of acute decompensated CHF, and the incidence rate was 19 episodes per 1000 patient-years. In addition to classical risk factors (age, female sex, obesity, diabetes, and previous history of CHF or coronary artery disease), creation of a successful AVF significantly increased the risk of CHF (OR=9.54, 95% CI: 4.84-18.81, P<.0001). In 47 out of 95 patients who developed CHF, a functioning AVF had previously been created, 92% of which were upper arm native AVF, with a median of 51 days between the surgical procedure and CHF episode. The mortality of patients with CHF was similar to that of the rest of the study patients, although unplanned dialysis initiation was significantly more frequent in those who developed CHF. CONCLUSIONS: Acute decompensated CHF episodes are common in pre-dialysis CKD patients. In addition to classical risk factors, pre-emptive AVF placement was strongly associated with the development of CHF.