Association of TLR4 Gene rs2149356 Polymorphism with Primary Gouty Arthritis in a Case-Control Study.docVIP

AssociationofTLR4Geners2149356Polymorphismwith PrimaryGoutyArthritisinaCase-ControlStudy Yu-FengQing1,Jing-GuoZhou1*,Quan-BoZhang2,Dong-ShengWang3,MinLi1,Qi-BinYang1 ,Cui- PingHuang1,LingYin1,Shu-YuePan1,Wen-GuangXie1,Meng-YunZhang1,Meng-JunPu1,MeiZeng4 1DepartmentofRheumatologyandImmunologyoftheAffiliatedHospital,NorthSichuanMedicalCollege,China,2DepartmentofgeriatricsoftheAffiliatedHospital, NorthSichuan MedicalCollege,China,3DepartmentofClinicalLaboratory,TheAffiliated HospitalofNorthSichuanMedicalCollege,China, 4Department ofgenetics, NorthSichuanMedicalCollege,China Abstract Background: The toll-like receptor (TLR)4-interleukin1b (IL1b) signaling pathway is involved in the monosodium urate (MSU)-mediatedinflammation.TheaimofthispresentstudywastodeterminewhethertheTLR4geners2149356SNPis associated with gouty arthritis (GA) susceptibility and whether rs2149356 SNP impacts the TLR4-IL1b signaling pathway moleculesexpression. Methods and Findings: The rs2149356 SNP was detected in 459GA patients and 669 control subjects (containing 459 healthy and 210 hyperuricemic subjects). Peripheral blood mononuclear cells (PBMCs) TLR4 mRNA and serum IL1b were measuredindifferentgenotypecarriers,andcorrelationsbetweenTLR4geneSNPandTLR4mRNA,IL1bwereinvestigated. The frequencies of the genotype and allele were significantly different between the GA and control groups (P,0.01, respectively). The TT genotype was associated with a significantly increased risk of GA (OR=1.88); this finding was not influencedbymakingadjustmentsforthecomponentsofpossibleconfounders(adjustedOR=1.96).TLR4mRNAandIL1b weresignificantlyincreasedintheTTgenotypefromacuteGApatients(P,0.05,respectively),andlipidsweresignificantly differentamongthreegenotypesintheGApatients(P,0.05,respectively). Conclusions:TheTLR4geners2149356SNPmightbeassociatedwithGAsusceptibility,andmightparticipateinregulating immune,inflammationandlipidmetabolism.Furtherstudiesarerequiredtoconfirmthesefindings. Citation:QingY-F,Z