title: Several polymorphisms of KCNQ1 gene are associated with plasma lipid levels in general Chinese populations.
abstract: BACKGROUND
  Potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) is thought to be an important candidate gene of diabetes. Several single nucleotide polymorphisms (SNPs) in a 40-kb linkage disequilibrium (LD) block in its intron 15 have been identified to be associated with diabetes in East Asian populations in recent genome-wide association studies. The aim of this study was to investigate whether KCNQ1 polymorphisms influence the levels of the metabolic phenotypes in general Chinese populations.
  
  
  RESULTS
  We investigated the associations of two SNPs (rs2237892 and rs2237895) in the aforementioned 40-kb LD block, a missense variant rs12720449 (P448R) in exon 10, and a synonymous variant rs1057128 (S546S) in exon 13 with metabolic phenotypes in a Uyghur population (n = 478) and replicated these associations in a Han population (n = 2,485). We found that rs2237892-T allele was significantly associated with decreased triglyceride levels (p(combined) = 0.001). The minor G allele of the rs12720449, with sharp difference of the allelic frequency between European and East Asian populations (0.2% versus 14%, respectively), was associated with a lower triglyceride levels than G allele in Uyghur subjects (p = 0.004), in Han subjects (p = 0.052), and in subjects of meta-analysis (p(combined) = 0.001). Moreover, the minor A allele of the rs1057128 was also associated with decreased triglyceride levels in meta-analysis (p(combined) = 0.010).
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first report associating a missense mutation of KCNQ1, rs12720449, with triglyceride levels. Rs2237892, representing the 40-kb LD block, is also associated with triglyceride levels in Han population. Further studies are required to replicate these findings in other East Asian populations.
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Xing-dong
authors.initials: XD
authors.lastname: Chen
authors.forename: Ya-jun
authors.initials: YJ
authors.lastname: Yang
authors.forename: Shu-yuan
authors.initials: SY
authors.lastname: Li
authors.forename: Qian-qian
authors.initials: QQ
authors.lastname: Peng
authors.forename: Li-juan
authors.initials: LJ
authors.lastname: Zheng
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002681:China; D003920:Diabetes Mellitus / Q000235:genetics; D005091:Exons; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014280:Triglycerides / Q000097:blood*
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D008055:Lipids; D014280:Triglycerides