Agouti-related protein promoter variant associated with leanness and decreased risk for diabetes in West Africans

Objective: The role of the central melanocortin system in the development of obesity has been extensively studied. Single-nucleotide polymorphisms (SNPs) within several candidate genes have been associated with food intake and obesity-related phenotypes; however, few of these associations have been replicated. SNPs in the agouti-related protein (AGRP) gene coding (Ala67Thr, 199G/A) and promoter (-38C/T) have been reported to be associated with body mass index (BMI), fat mass (FM) and percent body fat, in populations of European and African descent. In this study, we evaluated the association between the functional AGRP -38C/T promoter SNP and weight-related traits, namely BMI, FM and fat-free mass (FFM), as well as diabetes status. Design: An association study of the AGRP -38C/T SNP and indices of obesity and diabetes status. Subjects: A well-characterized population of 538 West Africans from Ghana and Nigeria recruited in the AADM (Africa America Diabetes Mellitus) study (mean age 52 years, 41.3% males, 71% diabetic). Measurements: Genotyping of the AGRP -38C/T SNP, BMI, FM, FFM and fasting plasma glucose. Results: Women carrying two copies of the variant T allele had significantly lower BMI (OR 0.47; 95% CI, 0.25-0.87). Also, men with at least one copy of the variant T allele were over two times less likely to be diabetic than other men (OR 0.44; 95% CI, 0.22-0.89). Conclusion: Our results replicate previous findings and implicate the AGRP -38C/T SNP in the regulation of body weight in West Africans.