Single-nucleotide polymorphisms and haplotype of CYP2E1 gene associated with systemic lupus erythematosus in Chinese population 英文参考文献.docVIP

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Single-nucleotide polymorphisms and haplotype of CYP2E1 gene associated with systemic lupus erythematosus in Chinese population 英文参考文献.doc

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Single-nucleotide polymorphisms and haplotype of CYP2E1 gene associated with systemic lupus erythematosus in Chinese population 英文参考文献

Liaoetal.ArthritisResearchTherapy2011,13:R11 /content/13/1/R11 RESEARCH ARTICLE OpenAccess Single-nucleotidepolymorphismsandhaplotype ofCYP2E1geneassociatedwithsystemiclupus erythematosusinChinesepopulation Ling-hongLiao1,HaoZhang2,Man-PoLai2,Shun-LeChen3,MadelineWu2,NanShen3* Abstract Introduction:CytochromeP-4502E1(CYP2E1)isanimportantmemberoftheCYPsuperfamily,whichisinvolved inthemetabolismandactivationofmanylowmolecularweighttoxiccompounds.Wetriedtoinvestigatethe possibleassociationofCYP2E1tagsinglenucleotidepolymorphisms(SNPs)withsusceptibilitytosystemiclupus erythematosus(SLE)inaChineseHanpopulation. Methods:ThecodingandflankingregionsoftheCYP2E1genewerescannedforpolymorphismsandtagSNPs wereselected.Atwo-stagecase-controlstudywasperformedtogenotypeatotalof876SLEpatientsand680 geographicallymatchedhealthycontrols(265casesand288controlsinstageIand611casesand392controlsin stageII).SLEassociationsofalleles,genotypesandhaplotypesweretestedbyageandsexadjustedlogistic regression.Thegenetranscriptionquantitationwascarriedoutforperipheralbloodmononuclearcell(PBMC) samplesfrom120healthycontrols. Results:TagSNPrs2480256wasfoundsignificantlyassociatedwithSLEinbothstagesofthestudy.The“A”allele wasassociatedwithslightlyhigherrisk(oddsratio(OR)=1.165,95%confidenceinterval(CI)1.073to1.265,P=2.75E- 4)and“A/A”genotypecarrierswerewithevenhigherSLErisk(OR=1.46495%CI1.259to1.702,P=7.48E-7).When combinedwithanothertagSNPrs8192772,weidentifiedhaplotype“rs8192772-rs2480256/TA”overpresentedinSLE patients(OR1.407,95%CI1.182to1.675,P=0.0001)andhaplotype“TG”overpresentedinthecontrols(OR0.771, 95%CI0.667to0.890,P=0.0004).Thegenetranscriptionquantitationanalysisfurtherprovedthedominanteffectof rs2480256asthe“A/A”genotypeshowedhighesttranscription. Conclusions:OurresultssuggesttheinvolvementofCYP2E1asasusceptibilitygeneforSLEintheChinese population. Introduction etiologyofSLE[1-4]ThesignificantdifferenceofSLEpre- Systemiclupuserythematosus(SLE(OMIM152700))isa valencebetweenAfricande