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Paraoxonase 1 polymorphisms and risk of myocardial infarction in women and men.

ABSTRACT: 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.

SUBMITTER: Mukamal KJ

PROVIDER: S-EPMC3827025 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Paraoxonase 1 polymorphisms and risk of myocardial infarction in women and men.

Mukamal Kenneth J KJ Pai Jennifer K JK Jensen Majken K MK Rimm Eric B EB

Circulation journal : official journal of the Japanese Circulation Society 20090515 7

<h4>Background</h4>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.<h4>Methods and results</h4>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 fo ...[more]

PMID: 19443958

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Project description:ObjectivesThere is conflicting evidence around the role of sex hormones with cardiovascular outcomes. The aim of this study was to examine the association of sex hormones with the risk of myocardial infarction (MI) in pre- and post-menopausal women, and men in the UK Biobank.MethodsThe UK Biobank is a prospective population-based cohort study, that recruited over 500,000 (aged 40-69 years) women and men between 2006 and 2010. Sex specific cox regression models, estimating hazard ratios (HRs) and women to men ratio of HRs (RHR) with respective 95% confidence intervals (CI), were used to model the association of sex hormones [oestrogen, testosterone, oestrogen: testosterone (O/T) ratio, sex hormone-binding globulin (SHBG) and the free androgen index (FAI)], measured at study baseline, with incident MI for women and men.ResultsData were from 479,797 participants [264,282 (55.1%) women] without a history of MI at study baseline. Over 12.5 years of follow-up, there were 4,908 MI events in women and 10,517 in men. Neither oestrogen nor testosterone were associated with MI in women and men after multiple adjustment. For men, but not women, a unit higher log-transformed O/T ratio was associated with a lower risk of MI 0.79 (0.65, 0.95) after adjustment for traditional CVD risk factors. The corresponding women to men RHR (95% CI) was 1.24 (0.99, 1.56). Higher SHBG (per unit) was also associated with a lower risk of MI in men 0.94 (0.89, 0.99), and not in women 1.02 (0.95, 1.09) after multiple adjustment, the corresponding women to men RHR (95% CI) was 1.09 (1.00, 1.18). Higher FAI was associated with a higher risk of MI in men 1.09 (1.02, 1.15), though not in women 0.97 (0.92, 1.02), the corresponding women to men RHR was 0.89 (0.82, 0.97). Finally, there were differential effects in the association of SHBG and FAI between pre- and post-menopausal women.ConclusionsA higher O/T ratio was associated with a lower risk of MI, and a higher FAI with a higher risk of MI after adjustment for CVD risk factors in men, but not in women. Thus, hormone ratios, rather than each alone, may play an important role in modulating the effect of MI.

Dataset Information

Paraoxonase 1 polymorphisms and risk of myocardial infarction in women and men.

Publications

Paraoxonase 1 polymorphisms and risk of myocardial infarction in women and men.

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