Author(s): Been LF, Ralhan S, Wander GS, Mehra NK, Singh J, et al.
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.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/21261977
Author(s): Gerich JE
Author(s): Stumvoll M, Goldstein BJ, van Haeften TW
Author(s): Dey L, Attele AS, Yuan CS
Author(s): Chen L, Magliano DJ, Zimmet PZ
Author(s): International Diabetes Federation
Author(s): Harcourt BE, Penfold SA, Forbes JM
Author(s): Wild S, Roglic G, Green A, Sicree R, King H
Author(s): Shera AS, Jawad F, Maqsood A
Author(s): Tattersall RB, Fajans SS
Author(s): Shields BM, Hicks S, Shepherd MH, Colclough K, Hattersley AT, et al.
Author(s): Kanwal SF, Fazal S, Muhammad Ismail, Nighat Naureen
Author(s): Velho G, Robert JJ
Author(s): Ben Khelifa S, Barboura I, Dandana A, Ferchichi S, Miled A
Author(s): Pittman WB, Acton RT, Barger BO, Bell DS, Go RC, et al.
Author(s): Matejkova-Behanova M
Author(s): Nambam B, Aggarwal S, Jain A
Author(s): Gale EA
Author(s): Fourlanos S, Dotta F, Greenbaum CJ, Palmer JP, Rolandsson O, et al.
Author(s): Cervin C, Lyssenko V, Bakhtadze E, Lindholm E, Nilsson P, et al.
Author(s): Owen KR, McCarthy MI
Author(s): Doria A, Patti ME, Kahn CR
Author(s): Yang L, Zhou X, Luo Y, Sun X, Tang Y, et al.
Author(s): Wheeler E, Barroso I
Author(s): McCarthy MI, Zeggini E
Author(s): Saxena R, Saleheen D, Been LF, Garavito ML, Braun T, et al.
Author(s): Prokopenko I, McCarthy MI, Lindgren CM
Author(s): Sanghera DK, Blackett PR
Author(s): Sladek R, Rocheleau G, Rung J, Dina C, Shen L, et al.
Author(s): Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research, Saxena R, Voight BF, et al.
Author(s): Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, et al.
Author(s): Wellcome Trust Case Control Consortium
Author(s): Steinthorsdottir V, Thorleifsson G, Reynisdottir I, Benediktsson R, Jonsdottir T, et al.
Author(s): Omori S, Tanaka Y, Takahashi A, Hirose H, Kashiwagi A, et al.
Author(s): Zeggini E, Scott LJ, Saxena R, Voight BF, Marchini JL, et al.
Author(s): Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, et al.
Author(s): Elbein SC, Das SK, Hallman DM, Hanis CL, Hasstedt SJ
Author(s): Ruchat SM, Elks CE, Loos RJ, Vohl MC, Weisnagel SJ, et al.
Author(s): Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, et al.
Author(s): Rees SD, Hydrie MZ, Shera AS, Kumar S, O'Hare JP, et al.
Author(s): Saxena R, Elbers CC, Guo Y, Peter I, Gaunt TR, et al.
Author(s): Morris AP, Voight BF, Teslovich TM, Ferreira T, Segrè AV, et al.
Author(s): Parra EJ, Below JE, Krithika S, Valladares A, Barta JL, et al.
Author(s): Tsai FJ, Yang CF, Chen CC, Chuang LM, Lu CH, et al.
Author(s): Xiang K, Wang Y, Zheng T, Jia W, Li J, et al.
Author(s): Das SK, Hasstedt SJ, Zhang Z, Elbein SC
Author(s): Love-Gregory LD, Wasson J, Ma J, Jin CH, Glaser B, et al.
Author(s): Silander K, Mohlke KL, Scott LJ, Peck EC, Hollstein P, et al.
Author(s): Helgason A, Pálsson S, Thorleifsson G, Grant SF, Emilsson V, et al.
Author(s): van Vliet-Ostaptchouk JV, Shiri-Sverdlov R, Zhernakova A, Strengman E, van Haeften TW, et al.
Author(s): van Hoek M, Dehghan A, Witteman JC, van Duijn CM, Uitterlinden AG, et al.
Author(s): Marquezine GF, Pereira AC, Sousa AG, Mill JG, Hueb WA, et al.
Author(s): Maeda S, Tsukada S, Kanazawa A, Sekine A, Tsunoda T, et al.
Author(s): Horikawa Y, Oda N, Cox NJ, Li X, Orho-Melander M, et al.
Author(s): Cho YM, Kim TH, Lim S, Choi SH, Shin HD, et al.
Author(s): Hu FB, Meigs JB, Li TY, Rifai N, Manson JE
Author(s): Moller DE
Author(s): Reitman ML, Schadt EE
Author(s): Holstein A, Seeringer A, Kovacs P
Author(s): Shu Y, Sheardown SA, Brown C, Owen RP, Zhang S, et al.
Author(s): Becker ML, Visser LE, van Schaik RH, Hofman A, Uitterlinden AG, et al.
Author(s): Avery P, Mousa SS, Mousa SA
Author(s): Aquilante CL
Author(s): Distefano JK, Watanabe RM
Author(s): Lebovitz HE
Author(s): Schroner Z, Javorsky M, Kozarova M, Tkac I
Author(s): Wolford JK, Vozarova de Courten B
