Common variants in TCF7L2 and CDKAL1 genes and risk of type 2 diabetes mellitus in Egyptians

AbstractIn this work we studied association of common variants in transcription factor 7-like 2 (TCF7L2) and cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) genes with type 2 diabetes mellitus (T2DM) in Egyptians.Subjects and methodsThis is a case–control study; 180 T2DM patients and 210 control subjects were genotyped for TCF7L2 rs7903146 and rs12255372 and CDKAL1 rs7756992 single nucleotide polymorphisms (SNPs) by TaqMan method on real time polymerase chain reaction system (real time-PCR).ResultsTCF7L2 rs12255372 and rs7903146 associated with T2DM (p=0.0001 and 0.003; respectively). The rs12255372 variant T allele associated with 2-fold increased risk for T2DM and TT genotype carriers were at 3.58-folds higher risk to develop T2DM than wild genotype (GG) carriers. Meanwhile, rs7903146 variant T allele associated with 1.6-fold increased risk for T2DM and TT genotype carriers were at 2.3-folds higher risk than wild genotype (CC) carriers. Both TCF7L2 SNPs significantly associated with T2DM under additive and dominant models and after adjustment for other covariates. On the other hand, CDKAL1 rs7756992 showed no significant association with T2DM under any genetic model. Both TCF7L2 SNPs were in strong LD (P=0.02; D′=0.85). Taking common TCF7L2 rs12255372/rs7903146 GC haplotype as reference, multivariate analysis confirmed the association of rs12255372 T allele-containing haplotypes (TC and TT) with T2DM. Haplotype TC associated with 6.32 times-higher risk for T2DM (95%CI=0.55–76.17, Pc=0.04) followed by haplotype TT which associated with 3.88 times-higher risk for the disease (95%CI=1.09–13.76, Pc=0.03).ConclusionTCF7L2 rs12255372 and rs7903146 common variants associate with T2DM risk in Egyptians