Investigating the Causal Association Between Helicobacter pylori Infection and Diabetic Nephropathy: A Two-Sample Mendelian Randomization Study.

Objective: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. This study investigated the potential causal association between Helicobacter pylori infection and DN. Methods: The two-sample Mendelian randomization (MR) methodology and public data on DN and H. pylori infection from genome-wide association studies (GWASs) were used. The primary MR analytical method was the inverse variance weighted (IVW), complemented by additional methods such as MR-Egger, weighted median, and weighted mode. Results were validated through extensive sensitivity analyses, including tests for pleiotropy (PhenoScanner), directionality (bidirectional MR and Steiger test), and heterogeneity. A false discovery rate (FDR) was applied to correct for multiple testing. Results: Among 7 H. pylori antibody markers, only genetically predicted catalase antibody levels showed a suggestive protective association with DN (odds ratio [OR] = 0.90, 95% confidence interval [CI]: 0.82-0.99, p = 0.03). However, this association did not withstand correction for multiple testing (P-FDR = 0.21). No significant causal effects were observed for other antibody markers. Sensitivity analyses found no evidence of horizontal pleiotropy and consistently supported a causal direction from H. pylori exposure to DN. Conclusion: Our findings provide suggestive evidence for a potential causal link between the host immune response to H. pylori catalase and a lower risk of DN. This specific, biologically plausible pathway warrants further investigation in larger, more diverse populations to confirm its potential role in the pathogenesis of DN.