HTR3A and HTR3E gene polymorphisms and diarrhea predominant irritable bowel syndrome risk: evidence from a meta-analysis.

Tangming Guan,Kefeng Wu,Yan Wang,Weiming Cai,Peipei Ouyang,Ting Li,Dong Huang,Xiaoli Ma,Huayan Chen

doi:10.18632/oncotarget.19682

Tangming Guan, Kefeng Wu + Show 7 more

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https://doi.org/10.18632/oncotarget.19682

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Journal: Oncotarget	Publication Date: Jul 29, 2017
Citations: 7	License type: cc-by

Affiliation: Guangdong Medical College

Abstract

Several studies have reported an association between serotonin receptor type 3 (5-HT3) subunit genes HTR3A (rs1062613) and HTR3E (rs62625044) and diarrhea predominant irritable bowel syndrome (IBS-D). However, the results remain inconclusive and controversial, particularly for the data derived from different ethnicities and genders. Therefore, we performed a meta-analysis to evaluate this association. All eligible case-control studies that met the search criteria were retrieved from multiple databases, and five case-control studies were included for detailed evaluation. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the strengths of the associations of HTR3A (rs1062613) and HTR3E (rs62625044) polymorphisms with IBS-D risk. Our results revealed statistically significant associations of the HTR3A (rs1062613, C/T) polymorphism with a decreased risk of IBS-D in all genetic models. Additionally, the HTR3E (rs62625044, G/A) polymorphism was also found to be significantly associated with a decreased risk of IBS-D in the allele and recessive models. Subgroup analysis revealed that these associations held true especially for Asians and female. In conclusion, this meta-analysis suggested that the C allele of HTR3A (rs1062613) and the G allele of HTR3E (rs62625044) are associated with a decreased risk of IBS-D.

Highlights

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorder characterized by abdominal discomfort, pain, and altered bowel habits; it may considerably reduce patients’ quality of life and work productivity, which affects more than 7 percent of people all around the world [1, 2]
All of the included studies were of high quality, as indicated by the Newcastle-Ottawa scale (NOS) scores of each study being above 6 points, and the genotype distributions in all of the controls were consistent with Hardy-Weinberg equilibrium (HWE), except one [6]
Several genetic association studies identified a novel association between HTR3 (HTR3A and HTR3E) and irritable bowel syndrome (IBS-D)

Summary

Introduction

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorder characterized by abdominal discomfort, pain, and altered bowel habits; it may considerably reduce patients’ quality of life and work productivity, which affects more than 7 percent of people all around the world [1, 2]. Genetic predisposition has been demonstrated in classical family/twin studies and epidemiological surveys, but unequivocal susceptibility genes have yet to be identified [2, 10]. Several genetic association studies identified the serotonin receptor type 3 (5-HT3) subunit genes HTR3A and HTR3E polymorphisms as being significantly associated with IBS ( IBS-D) [11,12,13,14]

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