Clinical Case Summary

A 53 year-old woman complained of chronic diarrhea, lack of appetitis and weight loss, that started two years before her admission. She described watery stools without bleeding or pus, as well as a 14 kg weight loss, but she had no fever, pruritus or night sweating. She had received a previous treatment for Graves’ disease during her pregnancy. Her physical examination was unremarkable, but she had a calprotectin fecal of 1028. Her last colonoscopy (performed 1 month before her admission) revealed an unspecific ileocolitis saving the sigmoid colon and the rectum, showing a friable and diffuse enanthematous mucous with some raised areas simulating a polypoid aspect. First she was empirically treated for parasitosis, and images were obtained, in addition to a wide range of laboratory tests. She presented a mild anemia associated with a thickened biliary tree and a pancreatic volume prominence with loss of its lobulations, as well as parietal enhancement of the ascending colon and enlarged mesenteric lymph nodes with hypodense centers suggesting necrosis.Upper GI biopsies were negative for H pylori infection, but biopsies of the colons showed a diffuse atypical lymphoplasmacytic infiltrate in the lamina propria. Medications and infectios were ruled out, and a PET-CT scan showed diffuse thickened wall of the colons (particularly cecum and transverse colon), as well as a mild thickened biliary tree, an enlarged thyroid and both mesenteric and pericolic lymphadenopathies - all of these areas showed a glycolytic activity slightly increased. IgG4 disease was also excluded after a normal IgG4/IgG relation from biopsy samples. Finally, a immunophenotyping study of the colons' samples was conducted, confirming a MALT lymphoma. The patient received rituximab for 9 months and a tumor restaging was conducted afterwards. A post-treatment PET-CT showed complete remission of the disease, with no areas of abnormal glycolytic metabolism, in addition to a fecal calprotectin of 11mcg/g.

Introduction

Aims & Methods

To systematically review genetic association studies (GAS) on GERD conducted from 2012–2024 and perform a meta-analysis to assess the relationship between specific genetic polymorphisms and GERD susceptibility.
A comprehensive literature search was conducted using PubMed, Cochrane, ScienceDirect, Scopus, DisGENET, GWASCatalog, and HuGE Phenopedia databases. Inclusion criteria focused on case-control studies reporting complete genotypic and allele frequency data. Meta-analytical methods were applied to pooled data for SNPs meeting analysis thresholds, calculating odds ratios (ORs) with 95% confidence intervals (CIs) under multiple genetic models (dominant, recessive, additive, codominant). Heterogeneity and publication bias were assessed using statistical tests and funnel plots.

Results

From an initial 9788 titles, 16 GAS involving 132 variants across 105 genes met the inclusion criteria. Meta- analysis was performed on four polymorphisms with sufficient data. Among these, the GNB3 rs5443 C>T polymorphism demonstrated a significant association with GERD (OR = 2.24; 95% CI: 1.56–3.21; p < 0.001), indicating a dominant genetic model with a two-fold increased risk of GERD. Polymorphisms in TNF, IL1B, and CYP2C19 genes showed no statistically significant associations. Notably, the GNB3 gene's role implicates its involvement in brain-gut signaling and inflammatory pathways, contributing to GERD pathophysiology. Heterogeneity was low across most analyses, and publication bias could not be definitively assessed due to the limited number of studies.

Conclusion

Disclosure

No Conflict of Interest