BACKGROUND: 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. METHODS: 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. KEY RESULTS: 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.
BACKGROUND: 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. METHODS: 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. KEY RESULTS: 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.
Authors: Nikola Fritz; Sabrina Berens; Yuanjun Dong; Cristina Martínez; Stefanie Schmitteckert; Lesley A Houghton; Miriam Goebel-Stengel; Verena Wahl; Maria Kabisch; Dorothea Götze; Mauro D'Amato; Tenghao Zheng; Ralph Röth; Hubert Mönnikes; Jonas Tesarz; Felicitas Engel; Annika Gauss; Martin Raithel; Viola Andresen; Jutta Keller; Thomas Frieling; Christian Pehl; Christoph Stein-Thöringer; Gerard Clarke; Paul J Kennedy; John F Cryan; Timothy G Dinan; Eamonn M M Quigley; Robin Spiller; Caroll Beltrán; Ana María Madrid; Verónica Torres; Emeran A Mayer; Gregory Sayuk; Maria Gazouli; George Karamanolis; Mariona Bustamante; Xavier Estivil; Raquel Rabionet; Per Hoffmann; Markus M Nöthen; Stefanie Heilmann-Heimbach; Börge Schmidt; André Franke; Wolfgang Lieb; Wolfgang Herzog; Guy Boeckxstaens; Mira M Wouters; Magnus Simrén; Gudrun A Rappold; Maria Vicario; Javier Santos; Rainer Schaefert; Justo Lorenzo-Bermejo; Beate Niesler Journal: J Mol Med (Berl) Date: 2022-09-19 Impact factor: 5.606
Authors: Sandra Mohr; Nikola Fritz; Christian Hammer; Cristina Martínez; Sabrina Berens; Stefanie Schmitteckert; Verena Wahl; Malin Schmidt; Lesley A Houghton; Miriam Goebel-Stengel; Maria Kabisch; Dorothea Götze; Irina Milovač; Mauro D'Amato; Tenghao Zheng; Ralph Röth; Hubert Mönnikes; Felicitas Engel; Annika Gauss; Jonas Tesarz; Martin Raithel; Viola Andresen; Thomas Frieling; Jutta Keller; Christian Pehl; Christoph Stein-Thöringer; Gerard Clarke; Paul J Kennedy; John F Cryan; Timothy G Dinan; Eamonn M M Quigley; Robin Spiller; Caroll Beltrán; Ana María Madrid; Verónica Torres; Edith Pérez de Arce; Wolfgang Herzog; Emeran A Mayer; Gregory Sayuk; Maria Gazouli; George Karamanolis; Lejla Kapur-Pojskič; Mariona Bustamante; Raquel Rabionet; Xavier Estivil; André Franke; Wolfgang Lieb; Guy Boeckxstaens; Mira M Wouters; Magnus Simrén; Gudrun A Rappold; Maria Vicario; Javier Santos; Rainer Schaefert; Justo Lorenzo-Bermejo; Beate Niesler Journal: J Cell Mol Med Date: 2021-06-24 Impact factor: 5.310