Analysis of IL12B Gene Variants in Inflammatory Bowel Disease 英文参考文献.docVIP

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2017-05-11 发布于上海
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Analysis of IL12B Gene Variants in Inflammatory Bowel Disease 英文参考文献.doc

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Analysis of IL12B Gene Variants in Inflammatory Bowel Disease 英文参考文献

AnalysisofIL12BGeneVariantsinInflammatoryBowel Disease Ju¨rgenGlas1,2,3.,JuliaSeiderer1.,JohannaWagner1,2,TorstenOlszak1,4,ChristophFries1,2 , CorneliaTillack1,MatthiasFriedrich1,2,FlorianBeigel1,JohannesStallhofer1,ChristianSteib1, MartinWetzke1,2,5,BurkhardGo¨ke1,ThomasOchsenku¨hn1,JuliaDiegelmann1,2*,DarinaCzamara6, StephanBrand1* 1Department of Medicine II - Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany, 2Department of Preventive Dentistry and Periodontology, LMU, Munich,Germany,3DepartmentofHumanGenetics,Rheinisch-Westfa¨lischeTechnischeHochschule(RWTH),Aachen,Germany,4DivisionofGastroenterology,Brigham Women’sHospital,HarvardMedicalSchool,Boston,UnitedStatesofAmerica,5DepartmentofPediatrics,HannoverMedicalSchool,Hannover,Germany,6Max-Planck- InstituteofPsychiatry,Munich,Germany Abstract Background:IL12Bencodesthep40subunitofIL-12,whichisalsopartofIL-23.Recentgenome-wideassociationstudies identifiedIL12BandIL23Rassusceptibilitygenesforinflammatoryboweldisease(IBD).However,thephenotypiceffectsand potentialgene-geneinteractionsofIL12Bvariantsarelargelyunknown. Methodology/Principal Findings: We analyzed IL12B gene variants regarding association with Crohn’s disease (CD) and ulcerative colitis(UC). Genomic DNA from2196 individuals including 913 CD patients, 318 UC patients and 965 healthy, unrelatedcontrolswasanalyzedforfourSNPsintheIL12Bgeneregion(rs3212227,rrrs6887695).Our analysisrevealedanassociationoftheIL12BSNPrs6887695withsusceptibilitytoIBD(p=0.035;OR1.15[95%CI1.01–1.31] including a trend for rs6887695 for association with CD (OR 1.41; [0.99–1.31], p=0.066) and UC (OR 1.18 [0.97–1.43], p=0.092).CDpatients,whowerehomozygousC/CcarriersofthisSNP,hadsignificantlymoreoftennon-stricturing,non- penetrating disease than carriers of the G allele (p=6.861025; OR=2.84, 95% CI 1.66–4.84), while C/C homozygous UC patients had less often extensive colitis than G allele carriers (p=0.029; OR=0.36, 95% CI 0.14–0.92). In silico anal