Interaction of Folate Intake and the Paraoxonase Q192R Polymorphism with Risk of Incident Coronary Heart Disease and Ischemic Stroke: The Atherosclerosis Risk in Communities Study

PURPOSE: To investigate the potential interaction between folate intake and the paraoxonase 1 (PON1) Q192R polymorphism with the risk of incident coronary heart disease (CHD) and ischemic stroke in the Atherosclerosis Risk in Communities study, a population-based prospective cohort of cardiovascular disease in 15,792 white and African-American subject. METHODS: Race-stratified Cox proportional hazards models were performed to examine the interaction between folate intake and the PON1 Q192R polymorphism. RESULTS: A significant inverse association between folate intake and risk of incident CHD among white subjects was found (hazard rate ratio, 1.30; 95% confidence interval, 1.09-1.56; P = .004; folate intake <= 155 mu g vs >= 279 mu g, reference group). An interaction effect was observed between the dominant genetic model and folate intake with regards to incident ischemic stroke in white subjects (hazard rate ratio, 0.68; 95% confidence interval, 0.91-0.99; and 1.24 from 1st-4th quartile, respectively; P-trend = .05). CONCLUSIONS: There was an interaction between folate intake and PON1 Q192 polymorphism with regard to the risk of ischemic stroke in white subjects. Future studies should investigate the interaction between additional polymorphisms within the PON1 gene and genetic variants in other folate metabolizing genes with folate intake on the risk of incident CHD and stroke. Ann Epidemiol 2011; 21:815-823. (C) 2011 Elsevier Inc. All rights reserved.