Pathways to Injury in Chronic Pancreatitis Decoding the Role of the High-Risk SPINK1 N34S Haplotype Using Meta-Analysis 英文参考文献.docVIP

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Pathways to Injury in Chronic Pancreatitis Decoding the Role of the High-Risk SPINK1 N34S Haplotype Using Meta-Analysis 英文参考文献.doc

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Pathways to Injury in Chronic Pancreatitis Decoding the Role of the High-Risk SPINK1 N34S Haplotype Using Meta-Analysis 英文参考文献

PathwaystoInjuryinChronicPancreatitis:Decodingthe RoleoftheHigh-RiskSPINK1N34SHaplotypeUsing Meta-Analysis ElieAoun1,Chung-ChouH.Chang2,3,JuliaB.Greer1,GeorgiosI.Papachristou1,M.MichaelBarmada4, DavidC.Whitcomb1,4 * 1Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 2Department of General Internal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 3Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 4Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Abstract Background:Thecomplexinteractionsbetweenrecurrenttrypsin-mediatedpancreaticinjury,alcohol-associatedpancreatic injuryandSPINK1polymorphismsinchronicpancreatitis(CP)areundefined.WehypothesizethatCPoccursasaresultof multiplepathologicalmechanisms(pathways)thatareinitiatedbydifferentmetabolicorenvironmentalfactors(etiologies) and may be influenced differentially by downstream genetic risk factors. We tested this hypothesis by evaluating the differences in effect size of the high risk SPINK1 N34S haplotype on CP from multiple etiologies after combining clinical reportsofSPINK1N34Sfrequencyusingmeta-analysis. MethodsandFindings:ThePubmedandtheEmbasedatabaseswerereviewed.Westudied24reportsofSPINK1N34SinCP (2,421 cases, 4,857 controls) using reported etiological factorsas surrogates for pathways and multiplemeta-analyses to determine the differential effects of SPINK1 N34S between alcoholic and non-alcoholic etiologies. Using estimates of between-study heterogeneity, we sub-classified our 24 studies into four specific clusters. We found that SPINK1 N34S is stronglyassociatedwithCPoverall(OR11.00;95%CI:7.59–15.93),buttheeffectofSPINK1N34SinalcoholicCP(OR4.98, 95%CI:3.16–7.85)wassignificantlysmallerthaninidiopathicCP(OR14.97,95%C.I.=9.09–24.67)ortropicalCP(OR19.15, 9