Relationship between the polymorphisms in KCNQ1 and type 2 diabetes in Chinese Kazakh population

Abstract

ABSTRACT. Recently genome-wide association studies on East Asian populations reported an association between diabetes and several single nucleotide polymorphisms (SNPs) in a 40-kb linkage disequilibrium block in intron 15 of KCNQ1. However, the association between KCNQ1 variants and type 2 diabetes mellitus (T2DM) in Chinese Kazakh populations is unknown. We investigated the relationship between rs2237892 and rs2237895 SNPs in KCNQ1 and susceptibility to and clinical characteristics of T2DM in 100 Chinese Kazakh T2DM subjects and 100 healthy subjects. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism and the main anthropometric and biochemical parameters of individuals were assessed in the genotype groups (rs2237892: CC, CT, or TT, and rs2237895: AA, AC, or CC). Genotype distribution and allele frequencies of these two SNPs were not significantly different between T2DM and control groups (P > 0.05). The frequencies of CT and TT genotypes and T allele for the rs2237892 SNP in females with T2DM were significantly higher than that in the control group (genotype: P = 0.016, allele: P = 0.004). However, there were no significant differences among individuals with different genotypes with respect to the rs2237895 SNP (P > 0.05). The main anthropometric and biochemical parameters did not correlate with the rs2237892 or rs2237895 SNPs in the T2DM group (P > 0.05). Thus, the T allele-containing genotypes of the rs2237892 SNP in KCNQ1 may increase the susceptibility to T2DM in female Chinese Kazakh individuals, whereas the rs2237895 SNP may not be associated with T2DM in the Chinese Kazakh population.

Association of KCNQ1rs2237892C ⟶ T Gene with Type 2 Diabetes Mellitus: A Meta-Analysis

“…Nattachet et al found a significant correlation between rs2237892SNP and T2D under additive and recessive models [ 13 ]. It was proved that rs2237892SNP is associated with T2DM in Korean population and in Lebanese population [ 14 , 15 ], but Cui et al suggested that Chinese Kazakhs rs2237892SNP may not be associated with T2DM [ 7 ], which is consistent with our findings. The frequency of KCNQ1 rs2237892SNP in Asians noted by Liu et al is lower than that in Europeans (92-96%), and the gene KCNQ1 rs2237892SNP was not significantly associated with T2D in the original European genome-wide association study.…”

“…Nattachet et al found a significant correlation between rs2237892SNP and T2D under additive and recessive models [13]. It was proved that rs2237892SNP is associated with T2DM in Korean population and in Lebanese population [14,15], but Cui et al suggested that Chinese Kazakhs rs2237892SNP may not be associated with T2DM [7], which is consistent with our findings. In conclusion, our investigation cannot prove the association of KCNQ1 rs2237892SNP with T2DM in Asian populations, and the observation of the C allele as a risk allele for T2DM in non-Asian populations may be due to small sample sizes [16,17], taking into account that geographical or cultural barriers increase the genetic distance, functional genes or regulatory regions may be disturbed by independent sets of rare 6…”

“…KCNQ1 is commonly expressed in epithelial cells, and KCNQ1 expression was also observed in insulin-secreting INS-1 cells. The selective inhibitor chromanol 293B inhibited KCNQ1 potassium channel activity and significantly increased insulin secretion [ 5 ]; Yazdi et al demonstrated a significant association between KCNQ1 and T2DM [ 6 ], but, research showed there was no significant association between KCNQ1 and T2DM [ 7 ]; Liu et al and Yu et al performed meta-analysis of multiple loci in the KCNQ1 gene, and the results again demonstrated the association between KCNQ1 and T2DM [ 8 , 9 ], but these two papers introduced data from meta-analyses, respectively, and their strength of proof may be weakened.…”

KCNQ1 rs2237895 gene polymorphism increases susceptibility to type 2 diabetes mellitus in Asian populations

“…Previous studies have found that C allele carriers of the KCNQ1 gene rs2237895 may have an increased risk of developing T2DM[ 7 ]. rs2237895 is present in three genotypes in the population, AA, AC and CC.…”

“…The A gene is wild type and the C gene is mutant, and their gene frequencies in the population are approximately 66% and 34%[ 8 ]. A study by Cui et al [ 7 ] in Kazakhs living in China showed that rs2237895 single nucleotide polymorphism (SNP) of KCNQ1 gene was not significantly associated with T2DM. A study by Afshardoost et al [ 9 ] on Iranians also showed no significant association between rs2237895 and T2DM; while in a study by Khan et al [ 10 ] on Indians, they confirmed a significant association between the SNP of rs2237895 and T2DM.…”