1. Department of Endocrinology and Metabolism, The Second People's Hospital of Yunnan Province & The Fourth Affiliated Hospital of Kunming Medical University, Kunming 650021, Yunnan, China.
2. Department of Medicine, Dentistry and Healthy Science, The University of Melbourne, Melbourne VIC3010, Australia.
3. Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, Yunnan, China.
4. School of Clinical Medicine, Dali University, Dali 671000, Yunnan, China.
*These authors contributed equally to this work.
Background: Type 2 diabetes mellitus (T2DM) has a high global prevalence, and insufficient insulin secretion is one of the major reasons for its development. Therefore, investigating the association between T2DM and the single nucleotide polymorphisms (SNPs) in genes associated with insulin secretion is necessary.
Methods: T2DM (1,194) and nondiabetic (NDM) (1,292) subjects were enrolled and the ten single nucleotide polymorphisms (SNPs) in KCNQ1, ARAP1, and KCNJ11 associated with insulin secretion were genotyped in a Chinese population.
Results: Our data revealed that the rs2237897T allele in KCNQ1 is the protective allele for T2DM (P<0.001, OR=0.793; 95%CI: 0.705-0.893). However, the A allele of rs1552224 in ARAP1 may be a risk factor for T2DM (P=0.002, OR=12.070; 95% CI: 1.578-92.337). The haplotype analysis revealed that rs151290-rs2237892CC and rs2237895-rs2237897CC in KCNQ1 constitute the risk haplotype in T2DM development (P=0.010, OR=1.160; 95% CI: 1.037-1.299 and P=0.004, OR=1.192; 95% CI: 1.057-1.344). Moreover, rs2237895-rs2237897AT in KCNQ1 constitutes the protective haplotype in T2DM (P=0.001, OR=0.819; 95% CI: 0.727-0.923). In the inheritance models analysis, the rs2283228 (C/A-C/C) genotype is the protective factor compared to the A/A genotype (P=0.005, OR=0.79; 95% CI: 0.68-0.93). For rs2237897, the C/T-T/T genotype is the protective factor compared to the C/C genotype (P<0.001, OR=0.74; 95% CI: 0.63-0.87). Furthermore, when compared with the rs2237897 (C/T-T/T) genotype, rs2237897C/C genotype showed higher HbA1C levels (8.731±2.697 vs 9.282±2.921, P=0.001).
Conclusion: Our results revealed that genetic variations in KCNQ1 and ARAP1 were associated with T2DM susceptibility in a Chinese population.
Keywords: type 2 diabetes mellitus, single nucleotide polymorphisms