Genetic liability to rheumatoid arthritis could be associated with a lower risk of developing periodontitis in a Mendelian randomization study. Despite the link, researchers cautioned that the finding should be viewed as a preliminary genetic signal rather than evidence that rheumatoid arthritis protects against periodontitis.

Using a two-sample Mendelian randomization analysis, the researchers evaluated whether genetic susceptibility to rheumatoid arthritis (RA) may be associated with periodontitis risk in East Asian populations. They drew on genome-wide association study data from 22,515 patients, including 4,873 with RA and 17,642 controls. The researchers selected 13 genetic variants associated with RA and used them as instrumental variables to estimate the effect of genetically predicted RA liability on periodontitis risk in a separate data set of 212,453 patients that included 3,219 cases of periodontitis and 209,234 controls.

The primary inverse-variance weighted analysis found that genetically predicted RA liability was associated with approximately 7% lower odds of periodontitis. The researchers described the association as statistically significant but modest. Additional analyses using weighted median and Mendelian randomization–Egger methods produced estimates in the same direction, supporting the consistency of the finding across analytic approaches.

Sensitivity analyses did not identify evidence that the result was driven by bias from any individual genetic variant. The researchers found no evidence of directional horizontal pleiotropy or significant heterogeneity among the instrumental variables and reported that leave-one-out analyses showed no single variant materially influenced the overall estimate.

The researchers noted that the findings differ from much of the observational literature, which has generally reported that RA and periodontitis occur together more frequently than expected. They also cited a previous Mendelian randomization study conducted in a European population that found no significant causal association between the two conditions. According to the researchers, differences in ethnicity, genetic background, environmental exposures, lifestyle and dietary patterns, health care practices, and disease definitions may contribute to the differing findings across the study populations.

The observed effect was small and should be interpreted cautiously because the periodontitis phenotype in the BioBank Japan Project data set was based on a broad periodontal disease definition rather than detailed clinical staging, raising the possibility of disease misclassification. In addition, the analysis was limited to East Asian populations, which may restrict generalizability to other ancestries. The researchers also acknowledged that residual pleiotropy and possible overlap between the exposure and outcome data sets could not be completely excluded.

"This inverse association does not necessarily mean that RA is a protective factor for [periodontitis]; rather, it should be viewed as a preliminary genetic signal that requires confirmation in independent cohorts and further mechanistic investigation," wrote lead study author Xinyi Li, MD, of the Department of Endodontics and Operative Dentistry at the Hospital of Stomatology in Zhongshan, China, and colleagues.

The study authors reported no funding and no conflicts of interest.

Source: Medicine