This study was undertaken to confirm and extend our earlier observation that gender is a biological effect modifier of smoking-rheumatoid arthritis (RA) relationship in a diverse national survey sample in the United States.
Smoking history of 644 cases of RA and 1509 geographically matched general population controls were compared using weighted logistic regression.
There were 644 respondents with RA (cases) and 1509 geographically matched controls. Cases were significantly younger, less educated, more likely to be single and female than controls. Among cases 57% were smokers while among controls 49% smoked. Among women, after adjusting for age, hysterectomy had an age adjusted odds ratio 1.45, (95% CI 0.99-2.10) and menopause an adjusted odds ratio 1.18 (95% CI 0.99-2.10) were associated with smoking. In univariable analysis ever-smoking was associated with increased risk of RA (odds ratio 1.34, 95% CI 1.0-1.81). Among the strata of smokers, there was an increasing gradient of risk with increasing exposure to smoking (P = 0.041). In separate multivariable models, smoking increased the risk in men (odds ratio 2.29, 95% CI 1.35-3.90) while in women the risk was not elevated (odds ratio 0.98, 95% CI 0.67-1.42). After adjusting for the statistically significant interaction both female gender (odds ratio 2.30, 95% CI 1.39-3.83) and having ever smoked (odds ratio 2.31, 95% CI 1.36-3.94) emerged as significant risk factors for RA.
Gender interacts with smoking in by an unknown mechanism to lead to differential risk of RA.