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Variants in KCNQ1 increase type II diabetes susceptibility in South Asians: a study of 3,310 subjects from India and the US.

ABSTRACT: 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.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.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).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 ? cell function.

SUBMITTER: Been LF

PROVIDER: S-EPMC3037841 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Variants in KCNQ1 increase type II diabetes susceptibility in South Asians: a study of 3,310 subjects from India and the US.

Been Latonya F LF Ralhan Sarju S Wander Gurpreet S GS Mehra Narinder K NK Singh JaiRup J Mulvihill John J JJ Aston Christopher E CE Sanghera Dharambir K DK

BMC medical genetics 20110124

<h4>Background</h4>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 t ...[more]

PMID: 21261977

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Project description:Objective:The purpose of this study was to develop and test the feasibility of a culturally tailored Diabetes Prevention Programme (DPP) for US South Asians, a large population with high diabetes risk. Design:The South Asian Health and Prevention Education (SHAPE) study included: (1) focus group discussions with South Asian adults to understand views of lifestyle behaviours and diabetes prevention; (2) modification of the US DPP for South Asians and (3) a pilot, pre-post study to test the feasibility and impact of delivering the culturally tailored programme. Setting:The study was conducted in Atlanta, Georgia, USA. Focus group discussions and intervention classes were held at locations within the community (eg, South Asian restaurants, a public library, university classrooms, a South Asian owned physical therapy studio). Participants:The focus group discussions (n=17 with 109 individuals) included adults aged 25 years of older who self-identified as South Asian. Groups were stratified by age (25-40 years or older than 40 years) and sex. The SHAPE pilot study included 17 (76.5% male with a mean age of 46.9±12 years) South Asian adults aged 25 years or older with pre-diabetes and body mass index (BMI) >22 kg/m2. Results:Formative data from 17 focus group discussions and a community board guided the modification of the DPP curriculum to reflect cultural food preferences and include tools to leverage social support, create a stronger foundation in exercise and overcome culturally specific barriers. The SHAPE pilot study included 17 South Asian adults with pre-diabetes and BMI >22 kg/m2. There were positive changes in participants' weight, waist circumference, blood pressure, plasma lipids, HbA1c and other cardiometabolic markers postintervention and 55% of participants regressed to normoglycaemia. Conclusion:These results provide important information on the barriers faced by US South Asians in participating in 'standard' lifestyle change programs, indicate the feasibility of culturally tailored programmes and show positive impact of a culturally tailored programme for diabetes prevention in the South Asian population.

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Variants in KCNQ1 increase type II diabetes susceptibility in South Asians: a study of 3,310 subjects from India and the US.

Publications

Variants in KCNQ1 increase type II diabetes susceptibility in South Asians: a study of 3,310 subjects from India and the US.

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