Original reportIn Search of Susceptibility Genes for Type 2 Diabetes in West Africa: The Design and Results of the First Phase of the AADM Study
Introduction
Type 2 diabetes is already a major health threat in populations in developed countries and this global diabetes epidemic is also taking hold rapidly in the developing world 1, 2, 3. Recent estimates suggest that the number of adults with diabetes will rise from 135 million in 1995 to 300 million in the year 2025, with the majority of this increase occurring in developing countries (3). In the United States, the prevalence of type 2 diabetes for persons 20 years or older is 5.1% for diagnosed diabetes (10.2 million persons) and 2.7% for undiagnosed (5.4 million persons), for a total prevalence of 7.8%. This represents an estimated 15.6 million (7.5 million men and 8.1 million women) Americans with diabetes based on the 1997 US population data (4).
The distribution of diabetes varies considerably with age, sex and ethnicity. In the latest US national survey, the prevalence of diabetes rose from 1–2% at ages 20–39 years to 18–20% at ages 60–74 years (4). Ethnic minority populations including African-Americans, Hispanics, and Native Americans are particularly vulnerable 3, 4, 5, 6, 7, 8, 9. Among African-Americans, diabetes ranks as the third most common reported condition (9). Overall, the prevalence of diabetes in African-Americans and Mexican-Americans is about two times that of non-Hispanic whites (4). The prevalence of diabetes reaches 50% among Pima Indians (1).
Although there is limited information on the magnitude of the problem of diabetes in sub-Saharan Africa, rates as low as 0.8%, based on World Health Organization (WHO) criteria for oral glucose tolerance test (OGTT) (10) were reported recently among 875 urban adults in Ibadan, Nigeria (11). In East Africa, McLarty and associates observed a prevalence of 1.1% among the Bantus in Tanzania (12). In contrast, rates as high as 8% have been reported among the Xhosa tribe in Cape Town, South Africa (13). Despite low prevalence, the poor state of the economy of these countries and the resulting poor access to diabetic care has led to a proportionally greater rate of diabetes complications including retinopathy, nephropathy, and neuropathy.
Reports from twin and family studies, as well as increased risk due to positive family history, and evidence linking some form of diabetes to single gene defects support the general scientific thinking that diabetes is a multi-factorial disease with a strong genetic component 4, 14, 15, 16, 17, 18. The presence of deleterious genetic variants, each one of which is relatively weak, in combination with exposure to harmful environmental factors is believed to favor the development of diabetes 19, 20, 21.
Despite recent success in identification of the genes involved in some subtypes of type 2 diabetes, little is known about susceptibility genes for the common forms of type 2 diabetes 22, 23. Currently, one of the limiting factors in the search for diabetes susceptibility genes at the population level is the lack of large numbers of well-characterized pedigrees with good epidemiologic data and adequate quantities of high quality DNA for genetic analyses. Among African-Americans, the lack of well-characterized pedigrees is magnified several folds. This is especially unfortunate given the high rate of diabetes and associated complications reported in this ethnic group.
Our strategy is to develop a database containing demographic, epidemiologic and pedigree information in conjunction with physiologic intermediates and high quality DNA for whole genome scans and candidate gene studies. This international collaborative effort brings together the expertise of investigators from multiple disciplines including epidemiology, medicine, and genetics. Furthermore, the collaboration presents opportunities to scientists in sub-Saharan Africa to actively participate in human genome research and will in the future facilitate research activities directed at understanding the etiology of other common complex diseases.
Section snippets
Planning and Selection of Field Sites
In the spring of 1995, with the National Human Genome Research Institute (NHGRI) and the Office of Research on Minority Health (ORMH) support, a meeting was held at NIH to discuss the feasibility of studying the genetics of type 2 diabetes in African Americans. This meeting which was attended by endocrinologists, anthropologists, ethicists, and geneticists reached a consensus that it will be useful to study genetic risk factors in West Africans; the founding population of modern
Results and discussion
The first phase (pilot phase) of the AADM study was implemented to determine feasibility of a large-scale genetic study by investigators from Ghana and Nigeria in collaboration with US Scientists from the National Human Genome Research Institute at NIH and Howard University College of Medicine. In a nine-month period, all five West African sites either met or surpassed the recruitment goal of 15 sib-pairs affected with type 2 diabetes. The recruitment goal was reached before the scheduled end
Acknowledgements
Support for AADM study is provided by NIH grant No. 3T37TW00041–03S2 from the Office of Research on Minority Health. This project is also support in part by the National Human Genome Research Institute (NHGRI).
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