Association between Helicobacter pylori infection and rheumatoid arthritis: Results from the NHANES 1999-2000 and a Mendelian randomization study.

The relationship between Helicobacter pylori infection and rheumatoid arthritis (RA) remains controversial. Our study aimed to provide evidence regarding the association between H pylori infection and RA by analyzing data from the 1999 to 2000 National Health and Nutrition Examination Survey (NHANES) and conducting Mendelian randomization (MR) analyses. A weighted logistic regression analysis was performed to examine the relationship between H pylori infection and RA, utilizing data from NHANES for the years 1999 to 2000. Furthermore, a bidirectional MR analysis was executed to explore both the causal and reverse causal relationships between H pylori infection and seropositive as well as seronegative RA. The primary analysis utilized inverse variance weighted in conjunction with additional MR methodologies to corroborate the causal link between H pylori infection and RA. Additionally, assessments of heterogeneity, pleiotropy, and sensitivity analyses were conducted to evaluate the robustness of the results. The cross-sectional observational analysis and MR study did not provide clear evidence to support a correlation and causal relationship between H pylori infection and RA. A total of 550 participants were enrolled in our observational study in NHANES. Following the adjustment for various confounding variables, the analysis revealed no statistically significant association between H pylori infection and RA (odds ratio = 1.300; 95% confidence interval = 0.784-2.154, P = .416) . In the MR analysis, 7 common serum H pylori antibodies (anti-H pylori immunoglobulin G, GroEL, OMP, UREA, CagA, VacA, and Catalase) were not found to have a causal relationship with either seropositive or seronegative RA. Moreover, reverse MR analysis did not suggest a causal effect of seropositive or seronegative RA on H pylori infection. Results were robust across all sensitivity analyses.