Following repaglinide treatment, those T2DM patients with the rs2237892 T allele and rs2237895 C allele were more likely to have a positive response to repaglinide in terms of PPG levels (P < 0.05) than T2DM patients with the rs2237892 CC and rs2237895 AA genotypes.
Mild association of rs2237892 genotypes with T2DM was seen (P=0.014), highlighted by the significant association of the C/T genotype with increased T2DM risk (OR, 2.11; 95%CI, 1.25-3.53), after adjusting for BMI, gender, systolic and diastolic blood pressure, and serum lipid profile.
To examine the association of type 2 diabetes susceptibility loci and visceral fat accumulation, we genotyped 1279 Japanese subjects (556 men and 723 women), who underwent computed tomography for measurements of visceral fat area (VFA) and subcutaneous fat area (SFA) for the following single-nucleotide polymorphisms (SNPs): NOTCH2 rs10923931, THADA rs7578597, PPARG rs1801282, ADAMTS9 rs4607103, IGF2BP2 rs1470579, VEGFA rs9472138, JAZF1 rs864745, CDKN2A/CDKN2B rs564398 and rs10811661, HHEX rs1111875 and rs5015480, TCF7L2 rs7901695, KCNQ1 rs2237892, KCNJ11 rs5215 and rs5219, EXT2 rs1113132, rs11037909, and rs3740878, MTNR1B rs10830963, DCD rs1153188, TSPAN8/LGR5 rs7961581, and FTO rs8050136 and rs9939609.
Seven of the 29 single nucleotide polymorphisms (SNPs) examined were found to be associated with T2D risk at P ≤ 0.05, including rs6769511 (IGF2BP2), 2 SNPs in the WFS1 gene (rs4689388 and rs1801214), rs7903146 (TCF7L2), and 3 SNPs in the KCNQ1 gene (rs231362, rs2237892, and rs2237897).
In conclusion, KCNQ1 rs2237892 and rs2237895</span> polymorphisms were found to be associated with the therapeutic efficacy of repaglinide in Chinese T2DM patients.
The haplotype TCA containing the allele of rs2237892 (T), rs2283228 (C) and rs2237895 (A) was highly protective against T2D (Second model; OR = 0.17, P = 3.7 × 10(-11)).
Genome-wide association and meta-analysis in populations from Starr County, Texas, and Mexico City identify type 2 diabetes susceptibility loci and enrichment for expression quantitative trait loci in top signals.
The haplotype TCA containing the allele of rs2237892 (T), rs2283228 (C) and rs2237895 (A) was highly protective against T2D (Second model; OR = 0.17, P = 3.7 × 10(-11)).
Haplotype analysis further suggested that the T2D risk associated with KCNQ1 SNPs may be derived from 'G' allele of rs231362 and 'C' allele of rs2237895 and this appears to be mediated through β cell function.
In Chinese Han, we replicated the associations between 7 genetic loci and T2D, with risk allele-specific odds ratios (ORs) as follows: 1.27 (95% CI, 1.11-1.45; p = 0.0008) for CDKAL1-rs10946398, 1.26 (95% CI, 1.08-1.47; p = 0.003) for IGF2BP2-rs4402960, 1.19 (95% CI, 1.04-1.37; p = 0.009) for SLC30A8-rs13266634, 1.22 (95% CI, 1.06-1.41; p = 0.005) for CDKN2A/B-rs10811661, 1.20 (95% CI, 1.01-1.42; p = 0.03) for HHEX-rs5015480, 1.37 (95% CI, 1.19-1.69; p = 1.0 x 10(-4)) for KCNQ1-rs2237892, and 1.24 (95% CI, 1.01-1.52; p = 0.046) for FTO-rs8050136 after adjustment for age, gender, and body mass index.
We found that CDKAL1 (rs7756992), SLC30A8 (rs13266634, rs2466293), CDKN2A/2B (rs10811661) and KCNQ1 (rs2237892) were associated with T2DM with odds ratio from 1.21 to 1.35.
Four single nucleotide polymorphisms (SNPs) (rs2237892, rs2237895, rs2237897, and rs2283228) in KCNQ1 are reported to be associated with type 2 diabetes mellitus (T2DM), possibly caused by a reduction in insulin secretion and higher fasting glucose, but the results are inconsistent.
We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40).
We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40).
We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40).
SNPs rs2237897, rs2237892, and rs2283228 were significantly associated with type 2 diabetes (odds ratio [OR] 1.48, P = 3 x 10(-4); OR 1.38, P = 0.002; OR 1.31, P = 0.012, respectively).
Notably, the associations with type 2 diabetes were markedly attenuated after adjusting for HOMA-B (OR(rs2237892): 1.33 [1.05-1.68], P = 0.018; OR(rs2237895): 1.24 [1.00-1.54], P = 0.0524; OR(rs2237897): 1.22[0.98-1.53], P = 0.09).
The C-allele of KCNQ1 rs2237895 was associated with increased risk of type 2 diabetes in both the Malmö Case-Control (odds ratio 1.23 [95% CI 1.12-1.34]; P = 5.6 x 10(-6)) and the prospective (1.14 [1.06-1.22]; P = 4.8 x 10(-4)) studies.