The role of gene polymorphisms in the occurrence of gastroesophageal reflux disease: A systematic review and meta-analysis of genetic association studies.

BACKGROUND

Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder with multifactorial etiology, including genetic components. Despite numerous genetic association studies (GAS), the role of specific gene polymorphisms in GERD susceptibility remains unclear due to inconsistent findings.

AIMS: To systematically review GAS on GERD and conduct a meta-analysis to evaluate the association between specific gene polymorphisms and GERD risk.

METHODS

A systematic review of PubMed, Cochrane, ScienceDirect, Scopus, DisGENET, GWASCatalog, and HuGE Phenopedia databases (2012-2024) was conducted to identify GAS for GERD. Meta-analytical methods were used to synthesize the results.

RESULTS

21 GAS, including 27,783 GERD patients and 83,857 controls, were analyzed, focusing on 132 polymorphisms across 105 genes. Meta-analysis of seven studies revealed a significant association between GNB3 rs5443 C > T and increased GERD-like symptom phenotypes (ORp = 2.24, 95 % CI: 1.56-3.21), suggesting a dominant genetic model. No significant associations were found for TNF, IL1B, or CYP2C19. Heterogeneity and potential bias were observed in some analyses, necessitating cautious interpretation of the findings.

CONCLUSION

The findings support a robust association between GNB3 rs5443 C > T and susceptibility to GERD-like symptom phenotypes, suggesting a potential genetic predisposition. Additional large, well-characterized studies using standardized GERD definitions are needed to validate these results and elucidate the broader genetic landscape of the disease.