Abstract
BackgroundGenetic factors increase the risk of irritable bowel syndrome (IBS). Analysis of single nucleotide polymorphisms (SNPs) has been used in IBS patients, but the findings are inconsistent. The goal of this review was to synthesize all the published SNPs studies of IBS through meta-analysis to objectively evaluate the relevance of SNPs to IBS risks.MethodsIBS - related polymorphisms studies from 2000 to 2018 were searched. Pooled odds ratios with a 95% confidence interval for each SNP were evaluated through five genetic models. Ethnicity, ROME criteria and IBS subtypes were defined for subgroup analyze.ResultsTen relevant genes were evaluated. SNPs rs4263839 and rs6478108 of TNFSF15 associated with an increased risk of IBS; IL6 rs1800795 increased the risk for Caucasian IBS patients which diagnosed by Rome III criteria; and IL23R rs11465804 increased the risk for IBS-C patients. IL10 rs1800896 GG genotype associated with a decreased risk of IBS. No evidence supported the association of GNβ3 rs5443, TNFα rs1800629, and IL10 rs1800871 to IBS in this study.ConclusionsThis meta-analysis presents an in-depth overview for IBS SNPs analysis. It was confirmed that polymorphisms of TNFSF15 associated with increased IBS risk, while IL10 rs1800896 associated with decreased IBS risk. It might offer some insights into polymorphisms of inflammation factors which might affect IBS susceptibility. Moreover, the analysis also emphasizes the importance of diagnostic criteria and phenotype homogeneity in IBS genetic studies.
Highlights
Genetic factors increase the risk of irritable bowel syndrome (IBS)
Inclusion criteria and quality assessment All candidate studies were included if they met all the inclusion criteria as follow: (i) Case-control studies with subjects’ information, available allele frequency and no consanguinity between the case and control groups. (ii) Explicit ethnicity such as Caucasian or Mongolian. (iii) IBS diagnosis based on clinical examination and specific diagnostic criteria such as Rome I-III. (iv) Allele frequency meets Hardy-Weinberg equilibrium in healthy controls. (v) Largest sample size was included in reused data
The identified single nucleotide polymorphisms (SNPs) focus on neurotransmitter system (SLC6A4 5-HTTLPR, COMT rs4680 and β3 subunit of G-protein (GNβ3) rs5443) and the inflammation system (TNFα rs1800629, IL10 rs1800896, IL10 rs1800871, IL6 rs1800795, IL23R rs11465804, TNFSF15 rs4263839 and TNFSF15 rs6478108)
Summary
Genetic factors increase the risk of irritable bowel syndrome (IBS). Analysis of single nucleotide polymorphisms (SNPs) has been used in IBS patients, but the findings are inconsistent. The goal of this review was to synthesize all the published SNPs studies of IBS through meta-analysis to objectively evaluate the relevance of SNPs to IBS risks. Irritable bowel syndrome (IBS) is a predominant and common chronic gastrointestinal (GI) disorder presenting with recurrent abdominal pain accompanied with altered bowel habits. IBS has been a continually increasing trend worldwide, especially in developing countries. It leads to negative effects on the quality of life and the work efficiency of affected patients. Environmental and psychological factors, which may result in “brain-gut-axis” dysfunction [2], increase the risk of IBS. Due to the multifactorial origin and the elusive etiology of IBS, there is no consensus on diagnostic biomarkers/methods or curative therapy it
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