Common variants in the CRP gene in relation to longevity and cause-specific mortality in older adults: The Cardiovascular Health Study

Abstract

Common polymorphisms in the CRP gene are associated with plasma CRP levels in populationbased studies, but associations with age-related events are uncertain. A previous study of CRP haplotypes in older adults was broadened to include longevity and cause-specific mortality (all-cause, non-cardiovascular (nonCV), and cardiovascular (CV)). Common haplotypes were inferred from four tagSNPs in 4512 whites and five tagSNPs in 812 blacks from the Cardiovascular Health Study, a longitudinal cohort of adults over age 65. Exploratory analyses addressed early versus late mortality.Correspondence to: Lucia Hindorff, PhD, MPH, Cardiovascular Health Research Unit, 1730 Minor Avenue, Suite 1360, Seattle, WA, 98101, Telephone: 206-287-2808, FAX: 206-287-2662, Email: lah@u.washington.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptAtherosclerosis. Author manuscript; available in PMC 2009 April 1. Published in final edited form as:Atherosclerosis. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptCRP haplotypes were not associated with all-cause mortality or longevity overall in either population, but associations with all-cause mortality differed during early and late periods. In blacks, the haplotype tagged by 3872A (rs1205) was associated with increased risk of nonCV mortality, relative to other haplotypes (adjusted hazard ratio for each additional copy: 1.42, 95% CI: 1.07, 1.87). Relative to other haplotypes, this haplotype was associated with decreased risk of early but not decreased risk of late CV mortality in blacks; among whites, a haplotype tagged by 2667C (rs1800947) gave similar but nonsignificant findings. If confirmed, CRP genetic variants may be weakly associated with CV and nonCV mortality in older adults, particularly in self-identified blacks.Human longevity has in part a genetic basis, and inflammation genes are possible candidates 1 Circulating plasma levels of C-reactive protein, an acute phase reactant, are associated with diseases occurring in older age, both cardiovascular and noncardiovascular in origin 2 . That persons with higher plasma CRP levels are at greater risk of cardiovascular as well as noncardiovascular mortality 3, 4 suggests that CRP may be a candidate gene associated with human longevity.Circulating plasma CRP is partially regulated at the genetic level. Twin and family studies observe substantial heritability (20-40 percent) for CRP levels 5, 6 . Common and functional polymorphisms in the CRP gene have consistently been associated with inter-individual differences in plasma CR...

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mice: Multivariate Imputation by Chained Equations inR

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