{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:35:56Z","timestamp":1790019356516,"version":"4.0.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The potassium voltage-gated channel subfamily Q member 1 (<jats:italic>KCNQ1<\/jats:italic>) gene is recognized as a type 2 diabetes mellitus (T2DM) susceptibility gene. However, there is limited data regarding the association between KCNQ1 gene polymorphisms and gestational diabetes mellitus (GDM) susceptibility in China. To explore the association between <jats:italic>KCNQ1<\/jats:italic> gene polymorphisms and GDM susceptibility in a Chinese population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a case-control study including 500 pregnant women with GDM and 502 pregnant women with normal glucose tolerance (as controls). Blood samples and clinical data were collected. <jats:italic>KCNQ1<\/jats:italic> gene rs2237897, rs163184, rs151290, and rs2237892 were genotyped by SNPscan\u2122 genotyping assay. Using SPSS V.26.0, statistical analysis was performed to explore the association of <jats:italic>KCNQ1<\/jats:italic> gene polymorphisms with GDM and genotypes with blood glucose levels. Meta-analysis was further validated in different populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After being adjusted for confounding factors (age, parity, pre-pregnancy BMI (pre-BMI) and blood pressure) and Bonferroni correction, rs2237897 showed an association with decreased GDM risk in codominant heterozygous (CT vs. CC: OR = 0.537; 95% CI: 0.354-0.816; <jats:italic>P<\/jats:italic> = 0.004) and overdominant models (CT vs. CC+TT: OR = 0.533; 95% CI: 0.355-0.801; <jats:italic>P<\/jats:italic> = 0.002) in pregnant women aged &amp;lt; 30 years. However, rs2237892, rs151290, and rs163184 did not found associations with GDM after Bonferroni correction. Meta-analysis showed that rs2237892 was associated with decreased GDM risk in different races in dominant (TC+TT vs. CC: OR = 0.830; 95% CI: 0.699-0.985; <jats:italic>P<\/jats:italic> = 0.033), recessive (TT vs. CT+CC: OR = 0.733; 95% CI: 0.612-0.877; <jats:italic>P<\/jats:italic> = 0.001), codominant homozygous (TT vs. CC: OR = 0.679; 95% CI: 0.562-0.820; <jats:italic>P<\/jats:italic> &amp;lt; 0.001), codominant heterozygous (TC vs. CC: OR = 0.843; 95% CI: 0.753-0.945; <jats:italic>P<\/jats:italic> = 0.003) and allele models (T vs. C: OR = 0.852; 95% CI: 0.740-0.982; <jats:italic>P<\/jats:italic> = 0.027).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>KCNQ1<\/jats:italic> rs2237897 is associated with decreased GDM risk in a Chinese population. Although rs2237892 did not found association with GDM risk in our subjects, meta-analysis confirmed that rs2237892 is associated with reduced GDM risk across different populations. Further studies are needed to confirm these findings and elucidate the mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1451942","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T04:14:40Z","timestamp":1751429680000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Association between KCNQ1 gene polymorphisms and gestational diabetes mellitus susceptibility in a Chinese population"],"prefix":"10.3389","volume":"16","author":[{"given":"Yanying","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaotao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoli","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runmin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2337\/dc24-S002","article-title":"2. Diagnosis and classification of diabetes: standards of care in diabetes-2024","volume":"47","year":"2024","journal-title":"Diabetes Care"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-022-00734-y","article-title":"A global view of hypertensive disorders and diabetes mellitus during pregnancy","volume":"18","author":"Jiang","year":"2022","journal-title":"Nat Rev Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-1641","article-title":"Frequency of gestational diabetes mellitus at collaborating centers based on IADPSG consensus panel-recommended criteria: the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study","volume":"35","author":"Sacks","year":"2012","journal-title":"Diabetes Care"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.11628","article-title":"Association of gestational diabetes with maternal disorders of glucose metabolism and childhood adiposity","volume":"320","author":"Lowe","year":"2018","journal-title":"JAMA"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-5491.2003.00985.x","article-title":"Epidemiology of gestational diabetes mellitus and its association with Type 2 diabetes","volume":"21","author":"Ben-Haroush","year":"2004","journal-title":"Diabetes Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.03.083","article-title":"Voltage-gated K+ channel KCNQ1 regulates insulin secretion in MIN6 \u03b2-cell line","volume":"407","author":"Yamagata","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13781","article-title":"Celebrities in the heart, strangers in the pancreatic beta cell: Voltage-gated potassium channels Kv 7.1 and Kv 11.1 bridge long QT syndrome with hyperinsulinaemia as well as type 2 diabetes","volume":"234","author":"Lubberding","year":"2022","journal-title":"Acta Physiol (Oxf)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/ng.207","article-title":"Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus","volume":"40","author":"Yasuda","year":"2008","journal-title":"Nat Genet"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/ng.208","article-title":"SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations","volume":"40","author":"Unoki","year":"2008","journal-title":"Nat Genet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1335-6","article-title":"Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population","volume":"52","author":"Hu","year":"2009","journal-title":"Diabetologia"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1375-y","article-title":"Variants in KCNQ1 are associated with susceptibility to type 2 diabetes in the population of mainland China","volume":"52","author":"Liu","year":"2009","journal-title":"Diabetologia"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp294","article-title":"Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population","volume":"18","author":"Qi","year":"2009","journal-title":"Hum Mol Genet"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-008-0341-8","article-title":"Association between polymorphisms in SLC30A8, HHEX, CDKN2A\/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population","volume":"53","author":"Lee","year":"2008","journal-title":"J Hum Genet"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0246","article-title":"A variant in the KCNQ1 gene predicts future type 2 diabetes and mediates impaired insulin secretion","volume":"58","author":"Jonsson","year":"2009","journal-title":"Diabetes"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1393","article-title":"Association of KCNQ1 polymorphisms with the gestational diabetes mellitus in Korean women","volume":"95","author":"Shin","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1159\/000313918","article-title":"Polymorphisms in KCNQ1 are associated with gestational diabetes in a Korean population","volume":"74","author":"Kwak","year":"2010","journal-title":"Horm Res Paediatr"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1500-y","article-title":"Association of KCNQ1 gene polymorphism with gestational diabetes mellitus in a Chinese population","volume":"52","author":"Zhou","year":"2009","journal-title":"Diabetologia"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128901","article-title":"The rs2237892 polymorphism in KCNQ1 influences gestational diabetes mellitus and glucose levels: A case-control study and meta-analysis","volume":"10","author":"Ao","year":"2015","journal-title":"PLoS One"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ16-0431","article-title":"Association of common polymorphisms with gestational diabetes mellitus in Japanese women: A case-control study","volume":"64","author":"Kasuga","year":"2017","journal-title":"Endocr J"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/genes14040924","article-title":"Saudi community-based screening study on genetic variants in \u03b2-cell dysfunction and its role in women with gestational diabetes mellitus","volume":"14","author":"Alshammary","year":"2023","journal-title":"Genes (Basel)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/genes13081315","article-title":"KCNJ11 and KCNQ1 gene polymorphisms and placental expression in women with gestational diabetes mellitus","volume":"13","author":"Majcher","year":"2022","journal-title":"Genes (Basel)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126408","article-title":"Genetic determinants for gestational diabetes mellitus and related metabolic traits in Mexican women","volume":"10","author":"Huerta-Chagoya","year":"2015","journal-title":"PLoS One"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.12669\/pjms.326.11052","article-title":"KCNQ1 rs2237895 polymorphism is associated with Gestational Diabetes in Pakistani Women","volume":"32","author":"Fatima","year":"2016","journal-title":"Pak J Med Sci"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1159714","article-title":"Association of solute carrier family 30 A8 zinc transporter gene variations with gestational diabetes mellitus risk in a Chinese population","volume":"14","author":"Zeng","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-1848","article-title":"International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy","volume":"33","author":"Metzger","year":"2010","journal-title":"Diabetes Care"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2013.54.2.352","article-title":"Association of variants in PPAR\u03b3\u00b2, IGF2BP2, and KCNQ1 with a susceptibility to gestational diabetes mellitus in a Korean population","volume":"54","author":"Chon","year":"2013","journal-title":"Yonsei Med J"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15238","article-title":"Prevalence of obesity and associated complications in China: A cross-sectional, real-world study in 15.8 million adults","volume":"25","author":"Chen","year":"2023","journal-title":"Diabetes Obes Metab"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(21)00045-0","article-title":"Epidemiology and determinants of obesity in China","volume":"9","author":"Pan","year":"2021","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00636","article-title":"Incidence and risk factors of gestational diabetes mellitus: A prospective cohort study in Qingdao, China","volume":"11","author":"Li","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/dme.14885","article-title":"Common single-nucleotide polymorphisms combined with a genetic risk score provide new insights regarding the etiology of gestational diabetes mellitus","volume":"39","author":"Fang","year":"2022","journal-title":"Diabetes Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00247","article-title":"Genetic susceptibility to gestational diabetes mellitus in a Chinese population","volume":"11","author":"Cao","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2010.06.069","article-title":"Obesity and diabetes genetic variants associated with gestational weight gain","volume":"203","author":"Stuebe","year":"2010","journal-title":"Am J Obstet Gynecol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.21315\/mjps2021.19.2.9","article-title":"Meta-analysis of the genetic factors that predisposed asian women to gestational diabetes mellitus","volume":"19","author":"Bahktiar","year":"2021","journal-title":"Malaysian J Pharm Sci"},{"key":"B34","doi-asserted-by":"publisher","first-page":"13","DOI":"10.13404\/j.cnki.cjbhh.2014.02.005","article-title":"Association between KCNQ1 gene polymorphism and gestational diabetes mellitus in Zhongshan population","volume":"22","author":"Zhai","year":"2014","journal-title":"Chin J birth Health heredity"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1034","article-title":"A genome-wide association study of gestational diabetes mellitus in Korean women","volume":"61","author":"Kwak","year":"2012","journal-title":"Diabetes"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s43042-020-00054-8","article-title":"Update on the genetic and epigenetic etiology of gestational diabetes mellitus: a review","volume":"21","author":"Yahaya","year":"2020","journal-title":"Egyptian J Med Hum Genet"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12935","article-title":"Clinical and genetic characteristics of abnormal glucose tolerance in Japanese women in the first year after gestational diabetes mellitus","volume":"10","author":"Kasuga","year":"2019","journal-title":"J Diabetes Investig"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-005-1479-2","article-title":"Effects of I(Ks) channel inhibitors in insulin-secreting INS-1 cells","volume":"451","author":"Ullrich","year":"2005","journal-title":"Pflugers Arch"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.5808\/GI.2015.13.4.112","article-title":"Introns: the functional benefits of introns in genomes","volume":"13","author":"Jo","year":"2015","journal-title":"Genomics Inform"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1451942\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T04:14:41Z","timestamp":1751429681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1451942\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,2]]},"references-count":39,"alternative-id":["10.3389\/fendo.2025.1451942"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1451942","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,2]]},"article-number":"1451942"}}