Impact of KCNQ1, CDKN2A/2B, CDKAL1, HHEX, MTNR1B, SLC30A8, TCF7L2, and UBE2E2 on risk of developing type 2 diabetes in Thai population

Abstract

BackgroundSeveral type 2 diabetes (T2D) susceptibility loci identified via genome-wide association studies were found to be replicated among various populations. However, the influence of these loci on T2D in Thai population is unknown. The aim of this study was to investigate the influence of eight single nucleotide polymorphisms (SNPs) reported in GWA studies on T2D and related quantitative traits in Thai population.MethodsEight SNPs in or near the KCNQ1, CDKN2A/2B, SLC30A8, HHEX, CDKAL1, TCF7L2, MTNR1B, and UBE2E2 genes were genotyped. A case-control association study comprising 500 Thai patients with T2D and 500 ethnically-matched control subjects was conducted. Associations between SNPs and T2D were examined by logistic regression analysis. The impact of these SNPs on quantitative traits was examined by linear regression among case and control subjects.ResultsFive SNPs in KCNQ1 (rs2237892), CDK2A/2B (rs108116610, SLC30A8 (rs13266634), TCF7L2 (rs7903146) and MTNR1B (rs1387153) were found to be marginally associated with risk of developing T2D, with odds ratios ranging from 1.43 to 2.02 (p = 0.047 to 3.0 × 10–4) with adjustments for age, sex, and body mass index. Interestingly, SNP rs13266634 of SLC30A8 gene reached statistical significance after correcting for multiple testing (p = 0.0003) (p < 0.006 after Bonferroni correction). However, no significant association was detected between HHEX (rs1111875), CDKAL1 (rs7756992), or UBE2E2 (rs7612463) and T2D. We also observed association between rs10811661 and both waist circumference and waist-hip ratio (p = 0.007 and p = 0.023, respectively). In addition, rs13266634 in SLC30A8 was associated with glycated hemoglobin (p = 0.018), and rs7903146 in TCF7L2 was associated with high-density lipoprotein cholesterol level (p = 0.023).ConclusionOf the eight genes included in our analysis, significant association was observed between KCNQ1, CDKN2A/2B, SLC30A8, TCF7L2, and MTNR1B loci and T2D in our Thai study population. Of these, CDKN2A/2B, SLC30A8, and TCF7L2 genes were also significantly associated with anthropometric, glycemic and lipid characteristics. Larger cohort studies and meta-analyses are needed to further confirm the effect of these variants in Thai population.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0614-9) contains supplementary material, which is available to authorized users.

Association Between CDKAL1, HHEX, CDKN2A/2B and IGF2BP2 Gene Polymorphisms and Susceptibility to Type 2 Diabetes in Uttarakhand, India

“…In contrast, a study reported that WHR was significantly linked with CDKN2A/2B (rs10811661) risk allele among T2DM cases in the Chinese Han population with p = 0.032. 10 CDKN2A/2B gene may influence the risk of T2DM by decreasing the expression and proliferation of beta-cell. 23 IGF2BP2 gene has been recognized to be linked with reduced secretion of insulin and it has a significant role in T2DM pathogenesis.…”

“…Advancement in genomic data and technology have helped the genome-wide association studies (GWAS) in recognizing the susceptible genes of T2DM. 10 Numerous GWAS confirmed the association of susceptible genes with T2DM in or near CDK5 Regulatory Subunit Associated Protein 1-Like 1 (CDKAL1), PPARG, Solute Carrier Family 30 Member 8 (SLC30A8), TCF7L2, Melatonin Receptor 1b (MTNR1B), Potassium Voltage-Gated Channel, KQT-Like Subfamily, Member 1 (KCNQ1), Wolframin ER Transmembrane Glycoprotein (WFS1), Hepatocyte Nuclear Factor 1 Homeobox B (HNF1B), Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A/2B), Insulin-Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2), and Juxtaposed with Another Zinc Finger Protein 1 (JAZF1) among Asian and European population. [10][11][12] Chiefari et al studied the highmobility group A1 (HMGA1) gene variants in T2DM patients and controls in 3 populations of white European ancestry and found the association of functional HMGA1 variants in people with T2DM of European ancestry.…”

Association between single nucleotide polymorphisms in CDKAL1 and HHEX and type 2 diabetes in Chinese Population

“…However, in our study we did not observed any association between the rs7923837 and T2DM(P = 0.181) which may be explained by different environmental risk pro les between Europeans and Asians, different body composition and genetic backgrounds, different linkage disequilibrium patterns. This possibility also be supported by association study done for Thai population in 2018, Plengvidhya, N. et al found that no signi cant association could be concluded between rs7923837 on HHEX and T2DM [38].…”

tRNA Biology in the Pathogenesis of Diabetes: Role of Genetic and Environmental Factors

“…Below we provide a comprehensive review of these aspects with a particular focus on T2D. GWAS and replication studies have shown that polymorphic variants within the CD-KAL1 locus are strongly associated with increased T2D risk and reduced insulin secretion in different populations [83,84,[99][100][101][102][103][104][105][106][107][108][109][110]. All disease-associated SNPs are located in intron 5 of CDKAL1 [83].…”