%0 Journal Article
%T Variants in KCNQ1 increase type II diabetes susceptibility in South Asians: A study of 3,310 subjects from India and the US
%A Latonya F Been
%A Sarju Ralhan
%A Gurpreet S Wander
%A Narinder K Mehra
%A JaiRup Singh
%A John J Mulvihill
%A Christopher E Aston
%A Dharambir K Sanghera
%J BMC Medical Genetics
%D 2011
%I BioMed Central
%R 10.1186/1471-2350-12-18
%X 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 ¡Á 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 ¦Â cell function.The potassium voltage-gated channel, KQT-like subfamily member 1 (KCNQ1) is a member of 11 mammalian Kv channel families and has been extensively studied for its role in long QT syndrome. Mutations in KCNQ1 have been described to lead to cardiac long QT syndrome, Jervell and Lange-Nielsen syndrome, which are associated with cardiac conduction abnormalities and hearing loss [1]. KCNQ1 is expressed mainly in the heart, and to lesser extent in the pancreas, placenta, lung, liver, kidney, brain, and adipose tissue. In addition, KCNQ1 is expressed in vitro in insulin-secreting cel
%U http://www.biomedcentral.com/1471-2350/12/18