Several Polymorphisms of KCNQ1 Gene Are Associated with Plasma Lipid Levels in General Chinese Populations 英文参考文献.docVIP

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Several Polymorphisms of KCNQ1 Gene Are Associated with Plasma Lipid Levels in General Chinese Populations 英文参考文献.doc

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Several Polymorphisms of KCNQ1 Gene Are Associated with Plasma Lipid Levels in General Chinese Populations 英文参考文献

SeveralPolymorphismsofKCNQ1GeneAreAssociated withPlasmaLipidLevelsinGeneralChinesePopulations Xing-dongChen1,2.,Ya-junYang1,2.,Shu-yuanLi1,2,Qian-qianPeng1,2,Li-juanZheng1,2,LiJin1,2 ,Xiao- fengWang1,2 * 1StateKeyLaboratoryofGeneticEngineeringandMOEKeyLaboratoryofContemporaryAnthropology,SchoolofLifeSciencesandInstitutesofBiomedicalSciences, FudanUniversity,Shanghai,China,2ChinaMedicalCityInstituteofHealthSciences,Taizhou,Jiangsu,China Abstract Background: Potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) is thought to be an important candidategeneofdiabetes.Severalsinglenucleotidepolymorphisms(SNPs)ina40-kblinkagedisequilibrium(LD)blockin 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 metabolicphenotypesingeneralChinesepopulations. Methodology/Principal Findings: We investigated the associations of two SNPs (rs2237892 and rs2237895) in the aforementioned40-kbLDblock,amissensevariantrP448R)inexon10,andasynonymousvariantrs1057128 (S546S)inexon13withmetabolicphenotypesinaUyghurpopulation(n=478)andreplicatedtheseassociationsinaHan population (n=2,485). We found that rs2237892-T allele was significantly associated with decreased triglyceride levels (pcombined=0.001).TheminorGalleleoftherwithsharpdifferenceoftheallelicfrequencybetweenEuropean andEastAsianpopulations(0.2%versus14%,respectively),wasassociatedwithalowertriglyceridelevelsthanGallelein Uyghursubjects(p=0.004),inHansubjects(p=0.052),andinsubjectsofmeta-analysis(pcombined=0.001).Moreover,the minorAalleleofthers1057128wasalsoassociatedwithdecreasedtriglyceridelevelsinmeta-analysis(pcombined =0.010). Conclusions:Tothebestofourknowledge,thisisthefirstreportassociatingamissensemutationofKCNQ1 ,r with triglyceride levels. Rs2237892, representing the 40-kb LD block, is also associated