Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke

BACKGROUND: From initiation to plaque rupture, immune system components contribute to atherosclerosis. We investigated variation in inflammation-related genes – Interleukin (IL)-1β, IL-6, C-reactive protein (CRP), IL-10, IL-18, and the Tumor Necrosis Factor (TNF) superfamily [Lymphotoxin(LT)-α, TNF-...

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Autori principali: Bis, Joshua C., Heckbert, Susan R., Smith, Nicholas L., Reiner, Alexander P., Rice, Kenneth, Lumley, Thomas, Hindorff, Lucia, Marciante, Kristin D., Enquobahrie, Daniel, Monks, Stephanie A., Psaty, Bruce M.
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Lingua:English
Pubblicazione: 2007
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Accesso online:https://ncbi.nlm.nih.gov/pmc/articles/PMC2517173/
https://ncbi.nlm.nih.gov/pubmed/17981284
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1016/j.atherosclerosis.2007.09.031
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spelling pubmed-25171732009-05-01 Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke Bis, Joshua C. Heckbert, Susan R. Smith, Nicholas L. Reiner, Alexander P. Rice, Kenneth Lumley, Thomas Hindorff, Lucia Marciante, Kristin D. Enquobahrie, Daniel Monks, Stephanie A. Psaty, Bruce M. Atherosclerosis Article BACKGROUND: From initiation to plaque rupture, immune system components contribute to atherosclerosis. We investigated variation in inflammation-related genes – Interleukin (IL)-1β, IL-6, C-reactive protein (CRP), IL-10, IL-18, and the Tumor Necrosis Factor (TNF) superfamily [Lymphotoxin(LT)-α, TNF-α, LT-β] – with respect to nonfatal incident myocardial infarction (MI) or ischemic stroke risk. METHODS & RESULTS: A population-based case-control study recruited postmenopausal and/or hypertensive Group Health members aged 30 to 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 2,688 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-α promoter variants. 2007-11-05 2008-05 /pmc/articles/PMC2517173/ /pubmed/17981284 http://dx.doi.org/10.1016/j.atherosclerosis.2007.09.031 Text en
institution US National Library of Medicine
collection PubMed Central
language English
format Article
topic Article
spellingShingle Article
Bis, Joshua C.
Heckbert, Susan R.
Smith, Nicholas L.
Reiner, Alexander P.
Rice, Kenneth
Lumley, Thomas
Hindorff, Lucia
Marciante, Kristin D.
Enquobahrie, Daniel
Monks, Stephanie A.
Psaty, Bruce M.
Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke
description BACKGROUND: From initiation to plaque rupture, immune system components contribute to atherosclerosis. We investigated variation in inflammation-related genes – Interleukin (IL)-1β, IL-6, C-reactive protein (CRP), IL-10, IL-18, and the Tumor Necrosis Factor (TNF) superfamily [Lymphotoxin(LT)-α, TNF-α, LT-β] – with respect to nonfatal incident myocardial infarction (MI) or ischemic stroke risk. METHODS & RESULTS: A population-based case-control study recruited postmenopausal and/or hypertensive Group Health members aged 30 to 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 2,688 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-α promoter variants.
author Bis, Joshua C.
Heckbert, Susan R.
Smith, Nicholas L.
Reiner, Alexander P.
Rice, Kenneth
Lumley, Thomas
Hindorff, Lucia
Marciante, Kristin D.
Enquobahrie, Daniel
Monks, Stephanie A.
Psaty, Bruce M.
author_facet Bis, Joshua C.
Heckbert, Susan R.
Smith, Nicholas L.
Reiner, Alexander P.
Rice, Kenneth
Lumley, Thomas
Hindorff, Lucia
Marciante, Kristin D.
Enquobahrie, Daniel
Monks, Stephanie A.
Psaty, Bruce M.
author_sort Bis, Joshua C.
title Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke
title_short Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke
title_full Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke
title_fullStr Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke
title_full_unstemmed Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke
title_sort variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke
publishDate 2007
url https://ncbi.nlm.nih.gov/pmc/articles/PMC2517173/
https://ncbi.nlm.nih.gov/pubmed/17981284
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1016/j.atherosclerosis.2007.09.031
_version_ 1760730981086527488

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