Background: Previous studies of genetic variants of paraoxonase 1 (PON1) and coronary heart disease (CHD) have been conflicting and the modifying effects of lifestyle factors that affect PON1 activity are uncertain.
Methods and results: In parallel nested case-control studies, the prospective associations between PON1 polymorphisms Q192R and L55M and incident CHD were examined among participants in the Nurses' Health and Health Professionals Follow-up Studies. Women were followed for 8 years and men for 6 years, and 249 women and 266 men were documented with incident CHD. Neither polymorphism was associated with risk of CHD in either sex, and neither monounsaturated fat intake nor smoking interacted with genotype. Among women, there was a possible interaction of Q192R with alcohol intake (P interaction 0.06) and a suggestion of a similar interaction with the L55M genotype (P interaction 0.11). In analyses of both polymorphisms, alcohol intake > or =2.5 g/day was associated with lower risk among all women (odds ratio 0.45), except those with the Q192Q/L55M genotype (OR 1.33; P 3-way interaction 0.07).
Conclusions: PON1 polymorphisms are not associated with the risk of CHD nor do they interact with smoking or monounsaturated fat intake. A possible gene-alcohol interaction should be considered in future studies of PON1 and CHD.