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Genetic variants within the interleukin-1 gene cluster, and risk of incident myocardial infarction, and ischemic stroke: a nested case-control approach.

ABSTRACT: BACKGROUND AND PURPOSE:Recent findings implicating specific gene polymorphisms of the interleukin-1 superfamily gene cluster in the risk of developing athero-thrombotic disorders have generated great interest. However, to date, no prospective, genetic-epidemiological data are available. METHODS:Using DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we evaluated seven gene polymorphisms within the interleukin-1 gene cluster among 599 individuals who subsequently developed athero-thrombotic event and among 599 age- and smoking-matched individuals who remained free of reported cardiovascular disease during follow-up (341 incident myocardial infarction matched case-control pairs and 258 incident ischemic stroke matched case-control pairs). RESULTS:Overall, we observed little evidence of association between the polymorphisms tested and risk of incident athero-thrombotic events. Further adjustment for traditional cardiovascular risk factors yielded similar null findings. Of note, a modest association of rs1143623 with reduced risk of incident MI was found (recessive model: OR=0.455, 95% CI=0.215-0.960, uncorrected p=0.039). However, this finding was not corrected for multiple testing, and thus requires cautious interpretation. CONCLUSION:In contrast to prior retrospective studies, our prospective data suggest that the IL-1 cluster gene variation is not associated with risk of athero-thrombotic disorders.

SUBMITTER: Zee RY

PROVIDER: S-EPMC3817489 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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Genetic variants within the interleukin-1 gene cluster, and risk of incident myocardial infarction, and ischemic stroke: a nested case-control approach.

Zee Robert Y L RY Hennessey Hooman H Michaud Sherri E SE Ridker Paul M PM

Atherosclerosis 20080311 1

<h4>Background and purpose</h4>Recent findings implicating specific gene polymorphisms of the interleukin-1 superfamily gene cluster in the risk of developing athero-thrombotic disorders have generated great interest. However, to date, no prospective, genetic-epidemiological data are available.<h4>Methods</h4>Using DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we evaluated seven gene polymorphisms within the interleukin-1 gene cluster among 5 ...[more]

PMID: 18336824

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Project description:Background Few studies have investigated associations of acclerometer-based assessments of physical activity (PA) and sedentary behavior (SB) with incidence of cardiovascular disease (CVD) and its components. This prospective cohort study assessed the associations of accelerometer-measured PA and SB with total CVD, myocardial infarction, and ischemic stroke (IS). Methods and Results The authors included 16 031 women aged 62 years and older, free of CVD, with adherent accelerometer wear (≥10 hours/day for ≥4 days) from the Women's Health Study (mean age, 71.4 years [SD, 5.6 years]). Hip-worn ActiGraph GT3X+ accelerometers measured total volume of PA (total average daily vector magnitude), minutes per day of high-light PA and moderate to vigorous PA (MVPA), and SB. Women reported diagnoses of CVD, which were adjudicated using medical records and death certificates. Hazard ratios (HRs) were estimated for each exposure, and 95% CIs using Cox proportional hazards models were adjusted for accelerometer wear time, age, self-reported general health, postmenopausal hormone therapy, smoking status, and alcohol use. The hypothetical effect of replacing 10 minutes/day of SB or high-light PA with MVPA on CVD incidence was assessed using adjusted isotemporal substitution Cox models. Over a mean of 7.1 years (SD, 1.6 years) of follow-up, 482 total CVD cases, 107 myocardial infarction cases, and 181 IS cases were diagnosed. Compared with the lowest quartiles of total average daily vector magnitude and MVPA (≤60 minutes), women who were in the highest quartiles (>120 minutes of MVPA) had a 43% (95% CI, 24%-58%) and 38% (95% CI, 18%-54%) lower hazard of total CVD, respectively. Estimates were similar for total average daily vector magnitude and MVPA with IS, but PA was not associated with myocardial infarction overall. High-light PA was not associated with any CVD outcomes. Women who spent <7.4 hours sedentary per day had a 33% (95% CI, 11%-49%) lower hazard of total CVD compared with those who spent ≥9.5 hours sedentary. Replacing 10 minutes of SB with MVPA was associated with a 4% lower incidence of total CVD (HR, 0.96 [95% CI, 0.93-0.99]). Conclusions Accelerometer-assessed total PA and MVPA were inversely associated with total CVD and IS incidence, and SB was directly associated with total CVD; high-light PA was not related to CVD.

Dataset Information

Genetic variants within the interleukin-1 gene cluster, and risk of incident myocardial infarction, and ischemic stroke: a nested case-control approach.

Publications

Genetic variants within the interleukin-1 gene cluster, and risk of incident myocardial infarction, and ischemic stroke: a nested case-control approach.

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