Atherosclerosis · 2007
Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke.
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Bis Joshua C, Heckbert Susan R, Smith Nicholas L, Reiner Alexander P, Rice Kenneth, Lumley Thomas, Hindorff Lucia A, Marciante Kristin D, Enquobahrie Daniel A, Monks Stephanie A, Psaty Bruce M
Аннотация
BACKGROUND: From initiation to plaque rupture, immune system components contribute to atherosclerosis. We investigated variation in inflammation-related genes - interleukin (IL)-1beta, IL-6, C-reactive protein (CRP), IL-10, IL-18, and the tumor necrosis factor (TNF) superfamily [lymphotoxin(LT)-alpha, TNF-alpha, LT-beta] - with respect to nonfatal incident myocardial infarction (MI) or ischemic stroke risk.
METHODS AND RESULTS: A population-based case-control study recruited postmenopausal and/or hypertensive Group Health members aged 30-79 years. We chose a subset of single nucleotide polymorphisms (SNPs) to describe common gene-wide variation on the basis of linkage disequilibrium. 36 SNPs, describing 38 common haplotypes for 5 genes and a 3-gene cluster, were genotyped among 856 MI cases, 368 stroke cases, and 2688 controls. Associations of SNPs or PHASE-inferred haplotypes and risk were estimated using logistic regression; significance of gene-level associations was assessed with global Wald tests and permutation tests. Gene-wide IL-18 variation was associated with higher MI risk and an IL-1B haplotype was associated with lower stroke risk. In secondary analyses of SNPs, we observed associations of several IL-1B polymorphisms with risk of MI or stroke. IL-6, CRP, IL-10, and TNF superfamily gene variation was not associated with MI or stroke risk.
CONCLUSIONS: Our results support prior reports associating an IL-18 gene variant and MI risk, contribute additional evidence to reports of IL-1B and cardiovascular risk, and fail to confirm risk differences previously observed for CRP, IL-6, and TNF-alpha promoter variants.
METHODS AND RESULTS: A population-based case-control study recruited postmenopausal and/or hypertensive Group Health members aged 30-79 years. We chose a subset of single nucleotide polymorphisms (SNPs) to describe common gene-wide variation on the basis of linkage disequilibrium. 36 SNPs, describing 38 common haplotypes for 5 genes and a 3-gene cluster, were genotyped among 856 MI cases, 368 stroke cases, and 2688 controls. Associations of SNPs or PHASE-inferred haplotypes and risk were estimated using logistic regression; significance of gene-level associations was assessed with global Wald tests and permutation tests. Gene-wide IL-18 variation was associated with higher MI risk and an IL-1B haplotype was associated with lower stroke risk. In secondary analyses of SNPs, we observed associations of several IL-1B polymorphisms with risk of MI or stroke. IL-6, CRP, IL-10, and TNF superfamily gene variation was not associated with MI or stroke risk.
CONCLUSIONS: Our results support prior reports associating an IL-18 gene variant and MI risk, contribute additional evidence to reports of IL-1B and cardiovascular risk, and fail to confirm risk differences previously observed for CRP, IL-6, and TNF-alpha promoter variants.
Предметные рубрики MeSH
AdultAgedBrain IschemiaC-Reactive ProteinCase-Control StudiesCoronary Artery DiseaseFemaleGenetic Predisposition to DiseaseGenetic VariationHumansIncidenceInterleukin-10Interleukin-18Interleukin-1betaInterleukin-6Intracranial ArteriosclerosisLymphotoxin-betaMaleMiddle AgedMyocardial InfarctionRisk FactorsStrokeTumor Necrosis Factor-alphaVasculitis