Single Nucleotide Polymorphisms, Associated with Increased Risk of Irritable Bowel Syndrome with Predominant Constipation: A Meta Analysis

Abstract

Introduction. Genetic predisposition in combination with environmental factors and the patient’s psychological and emotional state play a key role in the development of irritable bowel syndrome (IBS). Studies of association between genetic polymorphisms and IBS can help in understanding the key pathophysiological mechanisms. To date, 11 meta-analyses on this issue have been published, however, none of them comprehensively summarize the data on the prevalence of genetic polymorphisms in IBS with predominant constipation (IBS-C).Aim: to summarize the published data on the impact of genetic polymorphisms on the risk of IBS-C.Materials and methods. A literature search was performed in the PubMed and Scopus databases. Identified studies were used for a meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Publications investigating genetic polymorphisms in patients with IBS-C were included in this analysis.Results. A total of 34 studies met the inclusion criteria. The collected data were sufficient to conduct a meta-analysis on polymorphisms of three of the listed genes: SLC6A4 (10 articles), GNB3 (5 articles), ADRA2A (4 articles). No significant association was found between the SLC6A4 (5-HTTLPR) polymorphism, GNB3 c.825C > T (rs5443) polymorphism and either IBS or IBS-C. It was found that ADRA2A 1291C>G polymorphism was significantly associated with both IBS and IBS-C.Conclusions. Our meta-analysis revealed that ADRA2A 1291C>G polymorphism was significantly associated with both IBS and IBS-C in the mixed population. Neither homozygous nor heterozygous variants of the SLC6A4 (5-HTTLPR) polymorphism and GNB3 C825T polymorphism were associated with either IBS-C or IBS as a whole.

Keywords

• genetic susceptibility
• genetic polymorphisms
• constipation
• irritable bowel syndrome
• 5-httlpr polymorphism