Key result
The 'G' risk allele of the KCNQ1 variant rs231362 was significantly associated with increased susceptibility to type 2 diabetes in South Asians (OR 1.24).
Why the study?
Do variants in the KCNQ1 gene increase susceptibility to Type II Diabetes in South Asians?
Case-Control (n=3,310)
Yes
Do variants in the KCNQ1 gene increase susceptibility to Type II Diabetes in South Asians?
Odds Ratio: 1.24 (95% CI 1.08–1.43)
p-value: p=0.002
Variants in the KCNQ1 gene, specifically rs231362 and rs2237895, are significantly associated with increased susceptibility to Type II Diabetes in South Asian populations.
Should not yet inform T2D risk assessment in South Asians; leaves open replication and functional validation of KCNQ1 variants.
BACKGROUND: Polymorphisms in intron 15 of potassium voltage-gated channel, KQT-like subfamily member 1 (KCNQ1) gene have been associated with type II diabetes (T2D) in Japanese genome-wide association studies (GWAS). More recently a meta-analysis of European GWAS has detected a new independent signal associated with T2D in intron 11 of the KCNQ1 gene. The purpose of this investigation is to examine the role of these variants with T2D in populations of Asian Indian descent from India and the US. METHODS: We examined the association between four variants in the KCNQ1 gene with T2D and related quantitative traits in a total of 3,310 Asian Indian participants from two different cohorts comprising 2,431 individuals of the Punjabi case-control cohort from the Sikh Diabetes Study and 879 migrant Asian Indians living in the US. RESULTS: Our data confirmed the association of a new signal at the KCNQ1 locus (rs231362) with T2D showing an allelic odds ratio (OR) of 1.24 95%CI [1.08-1.43], p = 0.002 in the Punjabi cohort. A moderate association with T2D was also seen for rs2237895 in the Punjabi (OR 1.14; p = 0.036) and combined cohorts (meta-analysis OR 1.14; p = 0.018). Three-site haplotype analysis of rs231362, rs2237892, rs2237895 exhibited considerably stronger evidence of association of the GCC haplotype with T2D showing OR of 1.24 95%CI [1.00-1.53], p = 0.001, permutation p = 8 × 10-4 in combined cohorts. The 'C' risk allele carriers of rs2237895 had significantly reduced measures of HOMA-B in the US cohort (p = 0.008) as well as in combined cohort in meta-analysis (p = 0.009). CONCLUSIONS: Our investigation has confirmed that the variation within the KCNQ1 locus confers a significant risk to T2D among Asian Indians. 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.
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Been et al. (2011) conducted a case-control in Type II diabetes (n=3,310). KCNQ1 variant rs231362 'G' allele vs. Reference allele was evaluated on Type II diabetes susceptibility (OR 1.24, 95% CI 1.08-1.43, p=0.002). The 'G' risk allele of the KCNQ1 variant rs231362 was significantly associated with increased susceptibility to type 2 diabetes in South Asians (OR 1.24).
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