The TCF7L2 rs7903146 (T) allele is associated with type 2 diabetes in urban Ghana: a hospital-based case-control study.
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.
Institute of Tropical Medicine and International Health, Charité, Universitätsmedizin Berlin, Spandauer Damm 130, 14050 Berlin, Germany. ina.danquah@dife.de.
Ina
I
Danquah
Till
T
Othmer
Laura K
LK
Frank
George
G
Bedu-Addo
Matthias B
MB
Schulze
Frank P
FP
Mockenhaupt
D000328:Adult; D000368:Aged; D000483:Alleles; D044383:Black People / Q000235:genetics*; D002154:Calpain / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005869:Ghana; D006239:Haplotypes; D006761:Hospitals; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D047495:PPAR gamma / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D000099161:Kcnj11 Channel
D002154:Calpain; D047495:PPAR gamma; D024661:Potassium Channels, Inwardly Rectifying; D058118:Transcription Factor 7-Like 2 Protein; D000099161:Kcnj11 Channel; C415197:calpain 10