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Background  Type 2 diabetes mellitus is increasing dramatically in sub-Saharan Africa, and genetic predisposition is likely involved in that. Yet, genetic variants known to confer increased susceptibility among Caucasians are far from being established in African populations. In Ghanaian adults, we examined associations of several of these polymorphisms with type 2 diabetes.    Methods  A hospital-based case–control study on type 2 diabetes (and hypertension) was conducted in Kumasi, Ghana.  TCF7L2  rs7903146,  KCNJ11  rs5219,  PPARγ  rs1801282 and  CAPN10  rs3842570, rs3792267, and rs5030952 were typed and associations with type 2 diabetes and phenotypic traits examined.    Results  675 patients with type 2 diabetes and 377 controls were compared. The minor allele frequency of the  TCF7L2  (T) allele was 0.33. In the multivariate model, this allele increased the risk of type 2 diabetes by 39% (95% confidence interval (CI), 1.07-1.81;  p  = 0.014). The minor alleles  KCNJ11  (G) and  PPARγ  (G) were practically absent (each, 0.001). Minor allele frequencies of  CAPN10  were for -43 (A) 0.11 and for -63 (C) 0.46. These variants showed no significant associations with type 2 diabetes. Two  CAPN10  haplotypes tended to protect against type 2 diabetes: 211 (aOR, 0.32; 95% CI, 0.03-1.92;  p  = 0.31) and 221 (aOR, 0.73; 95% CI, 0.48-1.10;  p  = 0.13).    Conclusions  In urban Ghana, the frequency of the  TCF7L2  rs7903146 (T) allele is comparable to the one in Caucasians; the association with type 2 diabetes is slightly weaker. The risk allele  KCNJ11  (G) and the protective allele  PPARγ  (G) are virtually absent. The potential influence of comparatively rare  CAPN10  haplotypes on type 2 diabetes risk in this population requires further evaluation. Large-scale genetic studies among native Africans aiming at fine-mapping the candidate genes are needed to identify the actual factors involved in their increased susceptibility to type 2 diabetes.

The TCF7L2 rs7903146 (T) allele is associated with type 2 diabetes in urban Ghana: a hospital-based case–control study