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As the common birthplace of all human populations, modern humans have lived longer on the African continent than in any other geographical region of the world. This long history, along with the evolutionary need to adapt to environmental challenges such as exposure to infectious agents, has led to greater genetic variation in Africans. The vast genetic variation in Africans also extends to genes involved in the absorption, distribution, metabolism and excretion of pharmaceuticals. Ongoing cataloging of these clinically relevant variants reveals huge allele-frequency differences within and between African populations. Here, we examine Africa's large burden of infectious disease, discuss key examples of known genetic variation modulating disease risk, and provide examples of clinically relevant variants critical for establishing dosing guidelines. We propose that a more systematic characterization of the genetic diversity of African ancestry populations is required if the current benefits of precision medicine are to be extended to these populations.
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Antiinfecciosos/uso terapéutico , Población Negra/genética , Enfermedades Transmisibles/tratamiento farmacológico , Enfermedades Transmisibles/genética , Evolución Molecular , Farmacogenética , Variantes Farmacogenómicas , África/epidemiología , Antiinfecciosos/efectos adversos , Antiinfecciosos/farmacocinética , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/transmisión , Frecuencia de los Genes , Variación Genética , Genotipo , Humanos , Fenotipo , Resultado del TratamientoRESUMEN
Pharmacogenomically relevant markers of drug response and adverse drug reactions are known to vary in frequency across populations. We examined minor allele frequencies (MAFs), genetic diversity (FST) and population structure of 1156 genetic variants (including 42 clinically actionable variants) in 212 genes involved in drug absorption, distribution, metabolism and excretion (ADME) in 19 populations (n=1478). There was wide population differentiation in these ADME variants, reflected in the range of mean MAF (ΔMAF) and FST. The largest mean ΔMAF was observed in African ancestry populations (0.10) and the smallest mean ΔMAF in East Asian ancestry populations (0.04). MAFs ranged widely, for example, from 0.93 for single-nucleotide polymorphism (SNP) rs9923231, which influences warfarin dosing to 0.01 for SNP rs3918290 associated with capecitabine metabolism. ADME genetic variants show marked variation between and within continental groupings of populations. Enlarging the scope of pharmacogenomics research to include multiple global populations can improve the evidence base for clinical translation to benefit all peoples.
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Farmacogenética , Grupos de Población , Pautas de la Práctica en Medicina , Frecuencia de los Genes , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
What is the relationship between the patterns of biological and sociocultural variation in extant humans? Is this relationship accurately described, or best explained, by the term 'race' and the schema of 'racial' classification? What is the relationship between 'race', genetics and the demographic groups of society? Can extant humans be categorized into units that can scientifically be called 'races'? These questions underlie the discussions that address the explanations for the observed differences in many domains between named demographic groups across societies. These domains include disease incidence and prevalence and other variables studied by biologists and social scientists. Here, we offer a perspective on understanding human variation by exploring the meaning and use of the term 'race' and its relationship to a range of data. The quest is for a more useful approach with which to understand human biological variation, one that may provide better research designs and inform public policy.
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Variación Genética , Grupos Raciales/genética , Demografía , Predisposición Genética a la Enfermedad , Genoma Humano , Humanos , InvestigaciónRESUMEN
AIMS/HYPOTHESIS: Hyperglycaemia disproportionately affects African-Americans (AfAs). We tested the transferability of 18 single-nucleotide polymorphisms (SNPs) associated with glycaemic traits identified in European ancestry (EuA) populations in 5,984 non-diabetic AfAs. METHODS: We meta-analysed SNP associations with fasting glucose (FG) or insulin (FI) in AfAs from five cohorts in the Candidate Gene Association Resource. We: (1) calculated allele frequency differences, variations in linkage disequilibrium (LD), fixation indices (F(st)s) and integrated haplotype scores (iHSs); (2) tested EuA SNPs in AfAs; and (3) interrogated within ± 250 kb around each EuA SNP in AfAs. RESULTS: Allele frequency differences ranged from 0.6% to 54%. F(st) exceeded 0.15 at 6/16 loci, indicating modest population differentiation. All iHSs were <2, suggesting no recent positive selection. For 18 SNPs, all directions of effect were the same and 95% CIs of association overlapped when comparing EuA with AfA. For 17 of 18 loci, at least one SNP was nominally associated with FG in AfAs. Four loci were significantly associated with FG (GCK, p = 5.8 × 10(-8); MTNR1B, p = 8.5 × 10(-9); and FADS1, p = 2.2 × 10(-4)) or FI (GCKR, p = 5.9 × 10(-4)). At GCK and MTNR1B the EuA and AfA SNPs represented the same signal, while at FADS1, and GCKR, the EuA and best AfA SNPs were weakly correlated (r(2) <0.2), suggesting allelic heterogeneity for association with FG at these loci. CONCLUSIONS/INTERPRETATION: Few glycaemic SNPs showed strict evidence of transferability from EuA to AfAs. Four loci were significantly associated in both AfAs and those with EuA after accounting for varying LD across ancestral groups, with new signals emerging to aid fine-mapping.
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Glucemia/genética , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/genética , Hiperglucemia/etnología , Hiperglucemia/genética , Insulina/genética , Adulto , Negro o Afroamericano/genética , Negro o Afroamericano/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Bases de Datos Genéticas/estadística & datos numéricos , delta-5 Desaturasa de Ácido Graso , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/etnología , Predisposición Genética a la Enfermedad/genética , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Sitios de Carácter Cuantitativo/genética , Factores de Riesgo , Población Blanca/genética , Población Blanca/estadística & datos numéricos , Adulto JovenRESUMEN
INTRODUCTION: Muscle biopsy is a minor surgical procedure that has been conducted over several decades in clinical practice. Over the years, the technique to implement this procedure has been modified to make it easier to perform and more tolerable for the patient. This study aimed to assess the feasibility of muscle biopsy as an office based procedure, by using a vacuum Assisted Biopsy System. METHOD: The procedure was successfully carried out on 57 individuals with/without diabetes, currently involved in the African American Diabetes Mellitus Study. One specimen was collected percutaneously from the vastus lateralis, under local anesthesia. A 16-gauge needle was used. RESULTS: Muscle biopsies were successfully carried out on all study participants. The study participants reported no complications after the procedure. CONCLUSION: The findings from our study show that muscle biopsy can be feasibly implemented as an office based procedure, involving minimal muscle invasion, less trauma, hospital stay time, and expenses.
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Biopsia con Aguja/métodos , Músculo Esquelético/patología , Adulto , Atención Ambulatoria , Biopsia con Aguja/instrumentación , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , VacioRESUMEN
AIMS/HYPOTHESIS: Chronically elevated blood glucose (hyperglycaemia) is the primary indicator of type 2 diabetes, which has a prevalence that varies considerably by ethnicity in the USA, with African-Americans disproportionately affected. Genome-wide association studies (GWASs) have significantly enhanced our understanding of the genetic basis of diabetes and related traits, including fasting plasma glucose (FPG). However, the majority of GWASs have been conducted in populations of European ancestry. Thus, it is important to conduct replication analyses in populations with non-European ancestry to identify shared loci associated with FPG across populations. METHODS: We used data collected from non-diabetic unrelated African-American individuals (n = 927) who participated in the Howard University Family Study to attempt to replicate previously published GWASs of FPG. Of the 29 single nucleotide polymorphisms (SNPs) previously reported, we directly tested 20 in this study. In addition to the direct test, we queried a 500 kb window centred on all 29 reported SNPs for local replication of additional markers in linkage disequilibrium (LD). RESULTS: Using direct SNP and LD-based comparisons, we replicated multiple SNPs previously associated with FPG and strongly associated with type 2 diabetes in populations with European ancestry. The replicated SNPs included those in or near TCF7L2, SLC30A8, G6PC2, MTNR1B, DGKB-TMEM195 and GCKR. We also replicated additional variants in LD with the reported SNPs in ZMAT4 and adjacent to IRS1. CONCLUSIONS/INTERPRETATION: We identified multiple GWAS variants for FPG in our cohort of African-Americans. Using an LD-based strategy we also identified SNPs not previously reported, demonstrating the utility of using diverse populations for replication analysis.
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Glucemia/genética , Ayuno/sangre , Estudio de Asociación del Genoma Completo/métodos , Negro o Afroamericano , Genotipo , Humanos , Desequilibrio de Ligamiento/genética , Población BlancaRESUMEN
The C825T single nucleotide polymorphism (SNP) in the guanine nucleotide-binding protein, beta polypeptide 3 ( GNB3) gene gives rise to a splice variant, GNB3s that has enhanced G protein activation and signal transduction activity. This variant has been reported to be associated with cardiovascular disease, diabetes and obesity. We studied this SNP in 95 healthy 18 to 30 year-old African American university students to determine its association with aerobic capacity and cardiorespiratory fitness as measured by peak oxygen consumption (VO (2)peak). We also tested the effect of heart rate variability (HRV) as an independent predictor of VO (2)peak. We tested the association of the SNP and HRV with VO (2)peak in a multivariate regression analysis with appropriate adjustments of covariates, under dominant and recessive models. We found a significant independent association of the 825T allele with VO (2)peak under the dominant model (beta-coef.=-0.101, P=0.0442). We also observed that HRV marginally influenced VO (2)peak. This finding suggests that GNB3 C825T polymorphism is associated with VO (2)peak which is influenced by autonomic modulation of heart rate in African Americans.
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Proteínas de Unión al GTP Heterotriméricas/genética , Consumo de Oxígeno/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Negro o Afroamericano/genética , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Análisis Multivariante , Análisis de Regresión , Transducción de Señal/genética , Estudiantes , Universidades , Adulto JovenRESUMEN
The 9th meeting of the African Society of Human Genetics, in partnership with the Senegalese Cancer Research and Study Group and the Human Heredity and Health in Africa (H3Africa) Consortium, was held in Dakar, Senegal. The theme was Strengthening Human Genetics Research in Africa. The 210 delegates came from 21 African countries and from France, Switzerland, UK, UAE, Canada and the USA. The goal was to highlight genetic and genomic science across the African continent with the ultimate goal of improving the health of Africans and those across the globe, and to promote the careers of young African scientists in the field. A session on the sustainability of genomic research in Africa brought to light innovative and practical approaches to supporting research in resource-limited settings and the importance of promoting genetics in academic, research funding, governmental and private sectors. This meeting led to the formation of the Senegalese Society for Human Genetics.
Le 9ème congrès de la Société Africaine de Génétique Humaine, en partenariat avec le Groupe d'Etude et de Recherche sur le Cancer (GERC) et le Consortium H3Africa, s'est tenu à Dakar, au Sénégal. Le thème était «Renforcer la recherche en Génétique Humaine en Afrique¼. Les 210 participants sont venus de 21 pays africains et de six non africains. L'objectif était de valoriser la génétique et la génomique à travers l'Afrique avec comme but ultime d'améliorer la santé des populations, et de promouvoir les carrières des jeunes chercheurs Africains. Une session sur la pérennité de la recherche génomique a révélé des approches innovantes et pratiques supportant la recherche dans des contextes de ressources limitées et l'importance de promouvoir la formation universitaire en génétique, le financement de la recherche par les gouvernements et le privé. Ce congrès conduisit à la création de la Société Sénégalaise de Génétique Humaine.
RESUMEN
Selenium has been shown to prevent cancer in a variety of animal model systems. Both epidemiological studies and supplementation trials have supported its efficacy in humans. However, the mechanism by which selenium suppresses tumor development remains unknown. Selenium is present in known human selenoproteins as the amino acid selenocysteine (Sec). Sec is inserted cotranslationally in response to UGA codons within selenoprotein mRNAs in a process requiring a sequence within the 3'-untranslated region (UTR), referred to as a Sec insertion sequence (SECIS) element. Recently, a human Mr 15,000 selenoprotein (Sep15) was identified that contains an in-frame UGA codon and a SECIS element in the 3'-UTR. Examination of the available cDNA sequences for this protein revealed two polymorphisms located at position 811 (C/T) and at position 1125 (G/A) located within the 3'-UTR. Here, we demonstrate significant differences in Sep15 allele frequencies by ethnicity and that the identity of the nucleotides at the polymorphic sites influences SECIS function in a selenium-dependent manner. This, together with genetic data indicating loss of heterozygosity at the Sep15 locus in certain human tumor types, suggests that Sep15 may be involved in cancer development, risk, or both.
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Regiones no Traducidas 3'/genética , Polimorfismo de Nucleótido Simple/fisiología , Proteínas/genética , Adulto , Población Negra/genética , ADN/sangre , ADN/genética , ADN de Neoplasias/genética , Femenino , Genotipo , Humanos , Pérdida de Heterocigocidad , Masculino , Neoplasias/genética , Selenoproteínas , Población Blanca/genéticaRESUMEN
The burden and aetiology of type 2 diabetes (T2D) and its microvascular complications may be influenced by varying behavioural and lifestyle environments as well as by genetic susceptibility. These aspects of the epidemiology of T2D have not been reliably clarified in sub-Saharan Africa (SSA), highlighting the need for context-specific epidemiological studies with the statistical resolution to inform potential preventative and therapeutic strategies. Therefore, as part of the Human Heredity and Health in Africa (H3Africa) initiative, we designed a multi-site study comprising case collections and population-based surveys at 11 sites in eight countries across SSA. The goal is to recruit up to 6000 T2D participants and 6000 control participants. We will collect questionnaire data, biophysical measurements and biological samples for chronic disease traits, risk factors and genetic data on all study participants. Through integrating epidemiological and genomic techniques, the study provides a framework for assessing the burden, spectrum and environmental and genetic risk factors for T2D and its complications across SSA. With established mechanisms for fieldwork, data and sample collection and management, data-sharing and consent for re-approaching participants, the study will be a resource for future research studies, including longitudinal studies, prospective case ascertainment of incident disease and interventional studies.
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With the changing distribution of infectious diseases, and an increase in the burden of non-communicable diseases, low- and middle-income countries, including those in Africa, will need to expand their health care capacities to effectively respond to these epidemiological transitions. The interrelated risk factors for chronic infectious and non-communicable diseases and the need for long-term disease management, argue for combined strategies to understand their underlying causes and to design strategies for effective prevention and long-term care. Through multidisciplinary research and implementation partnerships, we advocate an integrated approach for research and healthcare for chronic diseases in Africa.
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There are scant data from African populations on the association between beta-cell function and response to treatment with oral hypoglycaemic agents in Type 2 diabetes mellitus (T2DM). Fasting plasma C-peptide (FCP) and glucagon-stimulated C-peptide (GSCP) levels were measured in 116 Nigerians with T2DM at a university teaching hospital. After 9 months of follow-up and treatment, they were categorized into three groups based on response to treatment: (A) good control but not on maximum sulphonylurea (SU) therapy, (B) inadequate control but not on maximum SU therapy and (C) on maximum SU therapy+/-insulin or biguanide. Logistic regression models were used to investigate how well C-peptide levels predicted the subjects belonging to Group C who are likely to require insulin. The mean FCP and mean GSCP levels of Group C were significantly lower than in the other groups (p=0.024; p= <0.001 respectively). A GSCP cut-off value of < or =1.3 ng/mL predicted membership of Group C with 85% sensitivity and 89% specificity while a cut-off of < or =1.8 ng/mL was associated with 91% sensitivity and 66% specificity. In resource-poor settings where inadequate treatment are common, estimation of GSCP may be useful in predicting treatment response and should be weighed against the cost of inadequate therapy with higher morbidity and mortality.
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Diabetes Mellitus Tipo 2/fisiopatología , Islotes Pancreáticos/metabolismo , Glucemia/metabolismo , Índice de Masa Corporal , Tamaño Corporal , Péptido C/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ayuno , Femenino , Humanos , Masculino , Persona de Mediana Edad , NigeriaRESUMEN
OBJECTIVE: Prior studies have supported that waist circumference correlates better with visceral adipose tissue and is a better predictor of cardiovascular disease than are BMI and waist-to-hip ratio. In this study, we reexamine the role of waist size on the risk of hypertension and type 2 diabetes in African-origin populations from three contrasting environments. RESEARCH DESIGN AND METHODS: A cross-sectional survey was conducted of 5,042 men and women 25-74 years of age from Nigeria, Jamaica, and the U.S. The relationship between waist, blood pressure, and fasting blood glucose was assessed using multiple linear regression analyses. Logistic regression analyses using sex-specific empirical waist cut-points were used to determine the risks of hypertension and type 2 diabetes. RESULTS: Waist circumference was positively correlated with blood pressure and fasting blood glucose (P < 0.05). Increasing waist quartiles were significantly associated with higher risks of hypertension in the three populations, as estimated from age-adjusted odds ratios obtained from sex-specific logistic regression models. A highly elevated risk of type 2 diabetes-10-fold for Jamaican men and 23-fold for African-American women-was observed in the comparison of lowest to highest quartiles of waist circumference. CONCLUSIONS: Substantial reduction in hypertension and diabetes in men and women is achievable if the waist size is decreased in these populations. Intervention programs designed to reduce waist circumference through lifestyle modification, including exercise and diet, may have significant public health significance in reducing the incidence of hypertension and adult-onset diabetes in these populations.
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Población Negra , Composición Corporal/fisiología , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/epidemiología , Hipertensión/etnología , Hipertensión/epidemiología , Adulto , Negro o Afroamericano/estadística & datos numéricos , Anciano , Glucemia/análisis , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/etnología , Estudios Transversales , Femenino , Humanos , Jamaica/epidemiología , Masculino , Persona de Mediana Edad , Nigeria/epidemiología , Factores de Riesgo , Factores Sexuales , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: Rates of non-insulin-dependent diabetes mellitus have risen sharply in recent years among blacks in the U.S. and the U.K. Increases in risk have likewise been observed in the island nations of the Caribbean and in urban West Africa. To date, however, no systematic comparison of the geographic variation of NIDDM among black populations has been undertaken. RESEARCH DESIGN AND METHODS: In the course of an international collaborative study on cardiovascular disease, we used a standardized protocol to determine the rates of NIDDM and associated risk factors in populations of the African diaspora. Representative samples were drawn from sites in Nigeria, St. Lucia, Barbados, Jamaica, the United States, and the United Kingdom. A total of 4,823 individuals aged 25-74 years were recruited, all sites combined. RESULTS: In sharp contrast to a prevalence of 2% in Nigeria, age-adjusted prevalences of self-reported NIDDM were 9% in the Caribbean and 11% in the U.S. and the U.K. Mean BMI ranged from 22 kg/m2 among men in West Africa to 31 kg/m2 in women in the U.S. Disease prevalence across sites was essentially collinear with obesity, pointing to site differences in the balance between energy intake and expenditure as the primary determinant of differential NIDDM risk among these populations. CONCLUSIONS: In ethnic groups sharing a common genetic ancestry, these comparative data demonstrate the determining influence of changes in living conditions on the population risk of NIDDM.
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Población Negra , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/epidemiología , Adulto , África Occidental/etnología , Factores de Edad , Anciano , Constitución Corporal , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nigeria/epidemiología , Prevalencia , Factores de Riesgo , Distribución por Sexo , Reino Unido/epidemiología , Estados Unidos/epidemiología , Indias Occidentales/epidemiologíaRESUMEN
The frequency of the 235T and 174M alleles of the angiotensinogen gene, previously reported to be associated with hypertension in Caucasians and Japanese, was compared between 57 hypertensive African Americans and 130 normotensive African Americans sampled as part of a community survey of hypertension in the Chicago area. The frequency of the 235T allele was unrelated to hypertension status (cases, 83%, control subjects, 82%), as was true for the 174M allele. Compared with Caucasians, the frequency of the 235T allele was twice as high in this African American population, while the frequency of the 174M allele was similar. Even higher frequencies of the 235T allele (93%) were noted in a sample of 122 Nigerians. It appears that the 235T allele is very common in populations of West African origin, although we found no evidence that it confers risk of hypertension.
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Alelos , Angiotensinógeno/genética , Población Negra/genética , Hipertensión/genética , Adulto , Anciano , Secuencia de Bases , Chicago , ADN/sangre , ADN/genética , Femenino , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Nigeria/etnología , Sondas de Oligonucleótidos , Polimorfismo Genético , Valores de ReferenciaRESUMEN
Elevated blood pressure (BP) is more common in relatives of hypertensives than in relatives of normotensives, indicating familial resemblance of the BP phenotypes. Most published studies have been conducted in westernized societies. To assess the ability to generalize these estimates, we examined familial patterns of BP in a population-based sample of 510 nuclear families, including 1552 individuals (320 fathers, 370 mothers, 475 sons, and 387 daughters) from Ibadan, Nigeria. The prevalence of obesity in this community is low (body mass index: fathers, 21.6; mothers, 23.6; sons, 19.2; and daughters=21.0 kg/m2). The BP phenotype used in all analyses was created from the best regression model by standardizing the age-adjusted systolic blood pressure (SBP) and diastolic blood pressure (DBP) to 0 mean and unit variance. Heritability was estimated by use of the computer program SEGPATH from the most parsimonious model of "no spouse and neither gender nor generation difference" as 45% for SBP and 43% for DBP. The lack of a significant spouse correlation is consistent with little or no influence of the common familial environment. However, the heritability estimate of <50% for both SBP and DBPs reinforces the importance of the nonshared environmental effect.
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Población Negra/genética , Presión Sanguínea/genética , Hipertensión/genética , Adulto , Anciano , Índice de Masa Corporal , Salud de la Familia , Femenino , Genética de Población , Humanos , Hipertensión/epidemiología , Funciones de Verosimilitud , Masculino , Persona de Mediana Edad , Modelos Genéticos , Nigeria , Núcleo Familiar , Prevalencia , Programas InformáticosRESUMEN
Within the context of an international collaborative study of the evolution of hypertension in the black diaspora, we determined the allelic distribution of hypertension candidate genes for the renin-angiotensin system in three populations of African origin. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) and the M235T and T174M variants of the angiotensinogen (AGT) gene were examined in individuals from Nigeria, Jamaica, and the United States. Large differences in the prevalence of hypertension were recorded in door-to-door surveys, ranging from 16% in Nigeria to 33% in the United States. The frequency of the D allele was similar in all groups (54%, 59%, and 63% in Nigeria, Jamaica, and the United States, respectively). The 235T allele of the AGT gene was found in 81% of US and Jamaican blacks and 91% of Nigerians; very little variation was seen for the T174M marker. Despite large differences in hypertension rates, genetic variation at the index loci among these groups was modest. Overall, the frequency of the ACE*D allele was only slightly higher than that reported for European and Japanese populations, whereas the AGT 235T allele was twice as common. Compared with blacks in the western hemisphere, Nigerians had a higher frequency of the 235T allele, which is consistent with 25% European admixture in Jamaica and the United States. The results indicate the potential for etiologic heterogeneity in genetic factors related to hypertension across ethnic groups while suggesting that environmental exposures most likely explain the gradient in risk in the comparison among black populations.
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Angiotensinógeno , Hipertensión , Peptidil-Dipeptidasa A , Alelos , Angiotensinógeno/genética , Negro o Afroamericano , Población Negra , Hipertensión/etnología , Hipertensión/genética , Jamaica/etnología , Nigeria/etnología , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Estados Unidos/etnología , HumanosRESUMEN
The role of leptin in humans remains controversial. Leptin concentrations are highly correlated with body fat stores. We tested whether or not this relation was consistent across the range of body composition encompassing the lean as well as the obese. Individuals participating in community-based comparative research in Nigeria (n = 363), Jamaica (n = 372), and the United States (Maywood, IL; n = 699) had their plasma leptin concentrations and body compositions (with bioelectrical impedance analysis) measured. All participants identified themselves as being black. Body mass index (in kg/m2) ranged from 14 to 62. Large differences in mean plasma leptin were noted across populations for both men and women in Nigeria, Jamaica, and the United States, respectively (men: 2.8, 3.9, and 6.8 microg/L; women: 10.3, 18.6, and 27.7 microg/L). An exponential function fit the relation between percentage body fat or total fat mass and leptin for men and women at each site. For women and men the exponential function with either percentage body fat or total fat mass was of the same shape, but increased by a constant in women, yielding higher leptin concentrations than in men at every level of body fat. On the basis of this broad distribution of body composition, the data suggest an exponential response of leptin to increases in body fat stores, consistent with the development of leptin resistance in individuals developing obesity. These findings likewise confirm that men and women exhibit different set points in terms of leptin production.
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Población Negra , Composición Corporal , Proteínas/metabolismo , Tejido Adiposo , Adulto , Femenino , Humanos , Jamaica/etnología , Leptina , Masculino , Persona de Mediana Edad , Nigeria/etnología , Estados Unidos/etnologíaRESUMEN
BACKGROUND: Cardiovascular diseases represent the most common cause of death in the English-speaking Caribbean, and hypertension represents the most important predisposing condition. However, direct between-country comparative studies in the Caribbean have not previously been undertaken. OBJECTIVE: To obtain estimates of hypertension prevalence, awareness, treatment and control in three countries in the Caribbean. DESIGN: Population-based samples of adults aged 25-74 years in St Lucia, Barbados and Jamaica were surveyed regarding their cardiovascular health and their blood pressures were measured using a highly standardized protocol. A reference site was available from a collaborative study among blacks in metropolitan Chicago, Illinois, USA. RESULTS: At the 160/95 mmHg threshold, age-adjusted hypertension prevalence estimates for Jamaica, St Lucia and Barbados were 17.5, 18.3 and 21.5%, respectively, and 24.7, 26.9 and 27.9%, respectively, at the 140/90 mmHg threshold. The corresponding estimate for the Chicago site at the 140/90 mmHg threshold was 33.2%. The gradient in prevalence resembled the gradient in body mass index (25.7 kg/m2 in Jamaica to 29.3 kg/m2 in the USA). At the 160/95 mmHg threshold, the proportion of all hypertensives who were aware of their disease, pharmacologically treated and controlled was highest in Barbados (90, 85 and 72%, respectively) and lowest in St Lucia (74, 59 and 35%, respectively). Men, particularly those aged less than 55 years, were less likely to have their hypertension treated and controlled. CONCLUSIONS: Compared with estimates from earlier independent surveys, considerable progress has been made in hypertension detection and control in these countries, which should lead to sizable reductions in the burden of cardiovascular disease.
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Hipertensión/epidemiología , Adulto , Anciano , Barbados/epidemiología , Femenino , Humanos , Hipertensión/prevención & control , Hipertensión/terapia , Jamaica/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To examine the association between blood pressure, angiotensinogen levels, angiotensin converting enzyme activity and polymorphisms of the angiotensinogen and angiotensin converting enzyme genes in a population-based sample. METHOD: Five hundred participants were recruited in a house-to-house survey of three communities in metropolitan areas of Kingston and St Andrew, in Jamaica. Demographic data, anthropometric and blood pressure measurements were obtained for each participant during a brief clinic visit. Circulating levels of angiotensinogen and angiotensin converting enzyme activity were measured in venous blood samples. Polymorphisms of the angiotensinogen and angiotensin converting enzyme genes were determined. RESULTS: A weak association between angiotensinogen level, angiotensin converting enzyme activity and blood pressure was identified in this population, but substantial joint effect of angiotensin converting enzyme activity and angiotensinogen level on blood pressure was apparent. Variants of the angiotensinogen gene had inconsistent effects on blood pressure and on the risk of hypertension. Angiotensinogen level and angiotensin converting enzyme activity were significantly related to several measures of obesity, including body mass index, waist circumference and skin fold thickness. CONCLUSION: The angiotensinogen and angiotensin converting enzyme genetic variants which were studied appear to have only a modest relationship with blood pressure and associated anthropometric risk factors among blacks.