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Genetic association and epistatic interaction of the interleukin-10 signaling pathway in pediatric inflammatory bowel disease

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World Journal of Gastroenterology 2017年第27期23卷 4897-4909页

作者： Zhenwu Lin Zhong Wang John P Hegarty Tony R Lin Yunhua Wang Sue Deiling Rongling Wu Neal J Thomas Joanna Floros CHilD Research Department of Pediatricsthe Pennsylvania State UniversityCollege of Medicine Department of Radiology University of Pennsylvania Perelman School of Medicine Division of Biostatistics Department of Public Health Sciencethe Pennsylvania State UniversityCollege of Medicine Department of Surgery the Pennsylvania State UniversityCollege of Medicine Department of Obstetrics and Gynecology the Pennsylvania State UniversityCollege of Medicine

AIM To study the genetic association and epistatic interaction of the interleukin(il)-10 and il-10/stat3 pathways in pediatric inflammatory bowel disease(IBD). METHODS A total of 159 pediatric inflammatory IBD patients(Crohn's disease,n = 136; ulcerative colitis,n = 23) and 129 matched controls were studied for genetic association of selected single nucleotide polymorphisms(SNPs) of the il-10 gene and the genes il10 RA,il10 RB,stat3,and HO1,from the il-10/stat3 signaling pathway. As interactions between SNPs from different loci may significantly affect the associated risk for disease,additive(a) and dominant(d) modeling of SNP interactions was also performed to examine highorder epistasis between combinations of the individual SNPs. RESULTS The results showed that il-10 rs304496 was associated with pediatric IBD(P = 0.022),but no association was found for two other il-10 SNPs,rs1800872 and rs2034498,or for SNPs in genes il10 RA,il10 RB,stat3,and HO1. However,analysis of epistatic interaction among these genes showed significant interactions:(1) between two il-10 SNPs rs1800872 and rs3024496(additive-additive P = 0.00015,Bonferroni P value(Bp) = 0.003);(2) between il-10 RB rs2834167 and HO1 rs2071746(dominant-additive,P = 0.0018,Bp = 0.039); and(3) among il-10 rs1800872,il10 RB rs2834167,and HO1 rs2071746(additivedominant-additive,P = 0.00015,Bp = 0.005),as well as weak interactions among il-10 rs1800872,il-10 rs3024496,and il-10RA(additive-additive-additive,P = 0.003; Bp = 0.099),and among il10 RA,il10 RB,and HO1 genes(additive-dominant-additive,P = 0.008,Bp = 0.287).CONCLUSION These results indicate that both the il-10 gene itself,and through epistatic interaction with genes within the il-10/stat3 signaling pathway,contribute to the risk of pediatric IBD.

关键词：小儿科的煽动性的肠疾病 Interleukin-10 HO1 挑选核苷酸多型性 il10-stat3 小径 Epistatic 相互作用

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