Czogalla B, Schmitteckert S, Houghton L A, Sayuk G S, Camilleri M, Olivo-Diaz A, Spiller R, Wouters M M, Boeckxstaens G, Bermejo J Lorenzo, Niesler B
Institute of Human Genetics, Department of Human Molecular Genetics, University of Heidelberg, Heidelberg, Germany.
Neurogastroenterol Motil. 2015 May;27(5):717-27. doi: 10.1111/nmo.12548. Epub 2015 Mar 30.
To date, genetic-association studies of single nucleotide polymorphisms (SNP) in selected candidate genes with the symptom phenotype of irritable bowel syndrome (IBS) have typically involved hundreds to 2000 patients. SNPs in immune-related genes, such as cytokine and cytokine receptor encoding genes, have been reported to associate with IBS risk.
We conducted two independent case-control studies on 16 SNPs in IL1R1, IL4, IL6, IL8, IL10, IL23R, TNFA, and TNFSF15, one from the UK (194 patients and 92 healthy volunteers) and one from the USA (137 patients and 96 healthy volunteers). The main aim was to examine the relationship between inherited immunological diversity and IBS risk in a meta-analysis which included 12 additional, earlier studies. The meta-analysis comprised a total of 2894 patients (839 IBS-C, 1073 IBS-D, 502 IBS-M), and 3138 healthy volunteers with self-reported Caucasian ancestry.
The association of SNP rs4263839 (TNFSF15) was investigated in four studies and confirmed in the meta-analysis: IBS (OR 1.19, 95% CI 1.08-1.31), and IBS-C (OR 1.24, 95% CI 1.08-1.42). No additional SNPs residing in immunogenes associated with IBS symptom phenotypes.
CONCLUSIONS & INFERENCES: Our meta-analysis could not confirm a major role of most investigated SNPs, but a moderate association between rs4263839 TNFSF15 and IBS, in particular IBS-C. The analysis emphasizes the importance of definition and phenotype homogeneity, adequate study size and representativeness of the patient and control collective.
迄今为止，针对特定候选基因中的单核苷酸多态性（SNP）与肠易激综合征（IBS）症状表型进行的基因关联研究通常涉及数百至2000名患者。据报道，免疫相关基因中的SNP，如细胞因子和细胞因子受体编码基因，与IBS风险相关。
我们对IL1R1、IL4、IL6、IL8、IL10、IL23R、TNFA和TNFSF15中的16个SNP进行了两项独立的病例对照研究，一项来自英国（194例患者和92名健康志愿者），另一项来自美国（137例患者和96名健康志愿者）。主要目的是在一项荟萃分析中研究遗传免疫多样性与IBS风险之间的关系，该荟萃分析还纳入了另外12项早期研究。该荟萃分析共纳入2894例患者（839例IBS-C、1073例IBS-D、502例IBS-M）和3138名自我报告为白种人血统的健康志愿者。
四项研究对SNP rs4263839（TNFSF15）的关联性进行了研究，荟萃分析证实了该关联性：IBS（比值比1.19，95%置信区间1.08 - 1.31），以及IBS-C（比值比1.24，95%置信区间1.08 - 1.42）。免疫基因中没有其他SNP与IBS症状表型相关。
我们的荟萃分析无法证实大多数所研究SNP的主要作用，但rs4263839 TNFSF15与IBS，特别是IBS-C之间存在中度关联。该分析强调了定义和表型同质性、足够的研究规模以及患者和对照群体代表性的重要性。
