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Association studies between <jats:italic>KCNQ1<\/jats:italic> genetic variants and T2DM have been reported. The multifactorial disease T2DM is caused by interactions between genetic susceptibility and environmental factors. In this study, we examined the associations between the <jats:italic>KCNQ1<\/jats:italic> haplotype, which consists of the major alleles rs3852528, rs11024175, and rs2237892 (<jats:italic>ht<\/jats:italic>: ACC), and environmental factors such as alcohol consumption, which are related to the risk of T2DM, in two independent Korean populations. Data from health examination studies, i.e., HEXA (<jats:italic>n<\/jats:italic>\u2009=\u200950,357 subjects) and the Ansung\u2013Ansan community-based Korean cohort study (<jats:italic>n<\/jats:italic>\u2009=\u20097603), were analyzed. In both cohorts, fasting blood glucose levels were significantly increased in moderate-to-heavy drinkers and carriers of the homozygous ACC haplotype. A significant association between the <jats:italic>KCNQ1<\/jats:italic> haplotype and alcohol consumption in the risk of diabetes was observed in the HEXA (OR 1.587; 95% CI 1.128\u20132.234) and Ansung\u2013Ansan (OR 2.165; 95% CI 1.175\u20133.989) cohorts compared with abstainers not carrying the <jats:italic>KCNQ1<\/jats:italic> haplotype. Associations of the <jats:italic>KCNQ1<\/jats:italic> haplotype with alcohol consumption and \u03b2-cell function were observed in the Ansung\u2013Ansan cohort. Moderate-to-heavy drinkers with the ACC haplotype had lower fasting insulin levels and mean 60\u00a0min insulinogenic index (IGI<jats:sub>60<\/jats:sub>) compared with light drinkers and abstainers not carrying the ACC haplotype. These findings indicate that <jats:italic>KCNQ1<\/jats:italic> variants play a synergistic role with alcohol consumption in the development of T2DM and impaired \u03b2-cell function.\n<\/jats:p>","DOI":"10.1038\/s41598-021-01399-9","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T11:04:19Z","timestamp":1636369459000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic effect between the KCNQ1 haplotype and alcohol consumption on the development of type 2 diabetes mellitus in Korean cohorts"],"prefix":"10.1038","volume":"11","author":[{"given":"Ji Young","family":"Park","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Gyu","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Ho","family":"Yun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye-Ja","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Ick","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"1399_CR1","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1677\/jme-06-0053","volume":"38","author":"AM Ackermann","year":"2007","unstructured":"Ackermann, A. 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