A genome-wide search for type 2 diabetes susceptibility genes in West Africans: the Africa America Diabetes Mellitus (AADM) Study.

The incidence of type 2 diabetes is growing rapidly, not only in developed countries but also worldwide. We chose to study type 2 diabetes in West Africa, where diabetes is less common than in the U.S., reasoning that in an environment where calories are less abundant, incident cases of type 2 diabetes might carry a proportionately greater genetic component. Through the Africa America Diabetes Mellitus (AADM) study, we carried out a genome-wide linkage analysis of type 2 diabetes in a cohort of 343 affected sibling pairs (691 individuals) enrolled from five West African centers in two countries (Ghana: Accra and Kumasi; Nigeria: Enugu, Ibadan, and Lagos). A total of 390 polymorphic markers were genotyped, and multipoint linkage analysis was conducted using the GENEHUNTER-PLUS and ASM programs. Suggestive evidence of linkage was observed in four regions on three chromosomes (12, 19, and 20). The two largest logarithm of odds scores of 2.63 and 1.92 for chromosomes 20q13.3 and 12q24, respectively, are particularly interesting because these regions have been reported to harbor diabetes susceptibility genes in several other populations and ethnic groups. Given the history of forced migration of West African populations during the slave trade, these results should have considerable relevance to the study of type 2 diabetes in African Americans.

Calpain-10 gene polymorphisms and type 2 diabetes in West Africans: the Africa America Diabetes Mellitus (AADM) Study.

PURPOSE: To investigate whether the three single nucleotide polymorphisms (SNPs), SNP-43, -56, and -63 of CAPN10 were associated with type 2 diabetes in a West African cohort. METHODS: A total of 347 diabetic subjects and 148 unaffected controls from four ethnic groups in two West African countries were enrolled in this study. After genotyping three SNPs of CAPN10 and one SNP from CYP19, the allele, genotype, and haplotype frequencies as well as the odds ratios were calculated to test their association with type 2 diabetes. RESULTS: None of the alleles or genotypes was associated with type 2 diabetes. Although statistical analysis indicated that haplotype 221 was associated with type 2 diabetes (OR, 3.765; 95% CI, 1.577-8.989) in the two ethnic groups of Nigeria, the same haplotype did not show any association with type 2 diabetes in the two ethnic groups in Ghana (OR, 0.906; 95% CI, 0.322-2.552). CONCLUSION: Considering the relatively low frequency of haplotype 221 and that none of the haplotypes including 221 was associated with any of the diabetes-related quantitative traits tested, it is concluded that SNP-43, -56, and -63 of the CAPN10 gene variants may play a limited role in the risk of type 2 diabetes risks in this cohort of West Africans.

Genetic epidemiology of hypertension: an update on the African diaspora.

Hypertension is a serious global public health problem, affecting approximately 600 million people worldwide. The lifetime risk of developing the condition exceeds 50% in most populations. Despite considerable success in the pharmacological treatment of hypertension in all-human populations, the health-care community still lacks understanding of how and why individuals develop chronically elevated blood pressure. This gap in knowledge, and the high prevalence of hypertension and associated complications in some populations of African descent, have led some to conclude that hypertension is a "different disease" in people of African descent. Despite considerable evidence from epidemiologic studies showing that blood pressure distribution in populations of the African diaspora spans the known spectrum for all human populations, theories in support of unique "defects" among populations of African descent continue to gain wide acceptance. To date, no known environmental factors or genetic variants relevant to the pathophysiology of human hypertension have been found to be unique to Black populations. However, available genetic epidemiologic data demonstrate differential distributions of risk factors that are consistent with current environmental and geographic origins. This review summarizes the available evidence and demonstrates that as the exposure to known risk factors for hypertension (eg, excess consumption of salt and calories, stress, sedentary lifestyle, and degree of urbanization) increases among genetically susceptible individuals, the prevalence of hypertension and associated complications also increases across populations of the African diaspora. This observation is true for all human populations.

Prevalence and determinants of diabetic retinopathy and cataracts in West African type 2 diabetes patients.

OBJECTIVE: To quantify the prevalence of, and risk factors for, diabetic retinopathy and cataracts in patients with type 2 diabetes, and their spouse controls, enrolled from 5 centers in 2 West African countries (Ghana and Nigeria). METHOD: The analysis cohort was made up of 840 subjects with type 2 diabetes, and their 191 unaffected spouse controls, who were enrolled and examined in Lagos, Enugu, and Ibadan, in Nigeria, and in Accra and Kumasi, in Ghana. A diagnosis of diabetic retinopathy was made only where a participant had a minimum of one microaneurysm in any field, as well as exhibiting hemorrhages (dot, blot, or flame shaped), and maculopathy (with or without clinically significant edema). RESULTS: Average duration of diabetes was 7.0 years, and mean age at diagnosis was 46.5 years. Prevalence of diabetic retinopathy was 17.9%. Cataracts were present in 44.9% of the patients with type 2 diabetes, and in 18.3% of spouse controls. The risk of developing retinopathy increased more than 3-fold for patients at the highest fasting plasma glucose (FPG) level (OR=3.4; 95% CI, 1.8-6.3), compared to patients at the lowest FPG level. The odds ratios for persons with diabetes for 10 years or more, compared to persons with diabetes for less than 5 years, was 7.3 (95% CI, 4.3-12.3) for retinopathy, and 2.6 (95% CI, 1.5-4.5) for cataracts. CONCLUSIONS: Cataracts were a more important cause of vision impairment than was diabetic retinopathy in this cohort. The prevalence of cataracts in patients with diabetes was more than twice that of their spouse controls, indicating that type 2 diabetes is an important risk factor for cataract formation. Individuals who developed type 2 diabetes at an earlier age were more likely to develop both diabetic retinopathy and cataracts. A strong positive association was observed between FPG level, duration of diabetes, and risk of retinopathy and cataracts. The low prevalence of retinopathy and cataracts observed within the first 5 years of diagnosis of diabetes in this cohort, suggests that intensive blood glucose control may reduce the risk of the development and progression of retinopathy and cataracts. In this regard, early eye examination, preferably at first presentation of elevated blood glucose, is highly recommended.

Investigation of the renin gene as a putative locus for essential hypertension (EH) in Vincentian African Caribbeans

Epidemiological studies have consistently reported a higher prevalence of essential hypertension in black people. Other data indicate that black people may have salt regulatory systems with low reserves which are unable to cope with moderate quantities of salt and respond to salt loading by increasing their blood pressures. Black people are therefore susceptible to the deleterious effects of salt. As some forms of EH may be related to defects in salt regulatory systems, we investigated association of the renin gene locus (the rate limiting enzyme in an important salt regulatory system) with EH in an ethnically homogenous group of black people of African origin (Summary)

The atrial natriuretic peptide gene and essential hypertension in African-Caribbeans from St. Vincent and the Grenadines

Atrial natriuretic peptide (ANP) which alters sodium balance, blood volume and vascular tone represents an important candidate for investigating the genetic basis of essential hypertension (EH). Accordingly, we have studied Bg11 and Xho1 restriction fragment length polymorphisms (RFLPs) of the ANP gene in 147 hypertensive, 141 normotensive and 67 population-based control subjects from a homogenous population of West African origin from St Vincent and the Grenadines. We found no association of either Bg11 and Xho1 RFLPs with EH. This study suggests that the ANP locus may not exert a major gene effect on EH amongst the black people of St. Vincent and the Grenadines.(AU)

Linkage of the angiotensin gene locus to human essential hypertension in African Caribbeans

The renin-angiotensin system regulates blood pressure and sodium balance. The angiotensinogen gene which encodes the key substrate within the system has been linked to essential hypertension in white Europeans. It has been suggested that people of West African ancestry may have a different genetic basis for hypertension. In this study we have tested whether there is linkage of the angiotensinogen to essential hypertension in African Caribbeans from St. Vincent and the Grenadines. DNA from 63 affected sibling pairs with hypertension was tested for linkage by analyzing whether there was excess allele sharing among sibling genotyped using an angiotensingogen dinucleotide repeat sequence. There was significant support for linkage (T = 3.07, P = 0.001) and association of this locus to hypertension (Xý = 50.2, 12 degrees of freedom, P ó 0.001). A DNA polymorphism which alters methionine to threonine at position 235 (M235T) within the angiotensinogen peptide has been associated previously with hypertension. However, we found no association of this variant with hypertension in this study. These findings provide support for linkage and association of the angiotensinogen locus to hypertension in African Caribbeans and suggest some similarities in the genetic basis of essential hypertension in populations of different ethnicity (AU)