Purpose: Type 2 diabetes mellitus (T2DM) has a high global prevalence, and the interaction of environmental factors and genetic factors may contribute to the risk of T2DM. We aimed to investigate the association between T2DM and the single nucleotide polymorphisms (SNPs) in genes (CDKAL1  and HHEX ) associated with insulin secretion.
Subjects and Methods: T2DM (n=1,169) and nondiabetic (NDM) (n=1,277) subjects were enrolled and the eight SNPs in CDKAL1  and HHEX  genes associated with insulin secretion were genotyped in a Chinese population using MassARRAY. Then, the association of these SNPs with T2DM was analyzed.
Results: Our results revealed that four SNPs (rs4712524, rs10946398, rs7754840 in CDKAL1 , and rs5015480 in HHEX ) showed significantly different distributions between the T2DM and NDM groups (P < 0.00625). The G allele of rs4712524 (P =0.004, OR=1.184; 95% CI=1.057– 1.327), C allele of rs10946398 (P < 0.001, OR=1.247; 95% CI=1.112– 1.398), and C allele of rs775480 in CDKAL1  (P < 0.001, OR=1.229; 95% CI=1.096– 1.387) functioned as risk alleles of T2DM. The C allele of rs5015480 in HHEX  (P < 0.001, OR=1.295; 95% CI=1.124– 1.493) was also the risk factor for T2DM. The haplotype analysis revealed that CDKAL1  haplotype rs4712524G-rs10946398C-rs7754840C-rs9460546G (P =0.001, OR=1.210; 95% CI=1.076– 1.360) and HHEX  haplotype rs1111875C-rs5015480C (P < 0.001, OR=1.364; 95% CI=1.180– 1.576) were the risk factors of T2DM.
Conclusion: Our results revealed that genetic variations in CDKAL1  and HHEX  were associated with T2DM susceptibility in Chinese population.
Keywords: association study, single nucleotide polymorphisms, CDKAL1 , HHEX , type 2 diabetes, Chinese population