The fat mass and obesity-associated (FTO) gene variant rs9939609 predicts long-term incidence of cardiovascular disease and related death independent of the traditional risk factors

OBJECTIVE AND METHODS: The impact of the rs9939609 FTO variant on cardiovascular events was investigated in the 19-year follow-up of subjects recruited to the OPERA study. RESULTS: A total of 212 cardiovascular disease (CVD) and 152 coronary heart disease (CHD) events or deaths occurred during follow-up. The logistic regression analysis revealed that among the AA genotype the incidence of CHD (OR 1.905; 95% CI 1.250-2.903, p = 0.001) and CVD (OR 1.849; 1.265-2.702, p = 0.003) events or death was significantly higher when adjusted for age, sex, and study group. After further adjustment with BMI, smoking status, systolic blood pressure, and low-density lipoprotein cholesterol, the higher incidence of CHD and CVD events or death among subjects with the AA genotype remained significant (OR 1.895; p = 0.002 and p = 0.004, respectively). In Cox regression analysis, the AA genotype displayed a higher rate of CVD and CHD death when the model was adjusted for sex, age, and study group (p = 0.006 and p = 0.046). FTO rs9939609 AA genotype improved the C-index of the final predictive model from 0.709 to 0.715. In reclassification analyses, the integrated discrimination index was significant 0.011 (p = 0.010). CONCLUSION: The AA genotype of FTO rs9939609 seems to be associated with a higher risk of CVD, and this phenomenon seems to be independent of the traditional risk factors for atherosclerosis.