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

Authors: Hindorff LA; Rice KM; Lange LA; Diehr P; Halder I; Walston J; Kwok P; Ziv E; Nievergelt C; Cummings SR; Newman AB; Tracy RP; Psaty BM; Reiner AP

Abstract: Common polymorphisms in the CRP gene are associated with plasma CRP levels in population-based 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, noncardiovascular (non-CV), 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. CRP 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 non-CV 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 non-CV mortality in older adults, particularly in self-identified blacks.

Keywords: African Americans/*genetics; Aged; C-Reactive Protein/*genetics; Cardiovascular Diseases/ethnology/genetics/mortality; Cause of Death; Cohort Studies; Female; Genetic Predisposition to Disease/*genetics; Haplotypes; Humans; Linear Models; Longevity/genetics; Male; Polymorphism, Single Nucleotide/*genetics; Proportional Hazards Models; United States
Journal: Atherosclerosis
Volume: 197
Issue: 2
Pages: 922-30
Date: Sept. 25, 2007
PMID: 17888441
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Citation:

Hindorff LA, Rice KM, Lange LA, Diehr P, Halder I, Walston J, Kwok P, Ziv E, Nievergelt C, Cummings SR, Newman AB, Tracy RP, Psaty BM, Reiner AP (2008) Common variants in the CRP gene in relation to longevity and cause-specific mortality in older adults: the Cardiovascular Health Study. Atherosclerosis 197: 922-30.



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