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. 2011 Oct;4(5):542-8.
doi: 10.1161/CIRCGENETICS.111.960146. Epub 2011 Aug 18.

The coronary artery disease-associated 9p21 variant and later life 20-year survival to cohort extinction

Ambarish Dutta  1 , William Henley, Iain A Lang, Anna Murray, Jack Guralnik, Robert B Wallace, David Melzer
Affiliations

The coronary artery disease-associated 9p21 variant and later life 20-year survival to cohort extinction

Ambarish Dutta et al. Circ Cardiovasc Genet. 2011 Oct.

Abstract

Background: Common variation at chromosome 9p21 (marked by rs10757278 or rs1333049) is associated with coronary artery disease (CAD) and peripheral vascular disease. A decreasing effect at older age was suggested, and effects on long-term mortality are unclear. We estimated 9p21 associations with CAD and all-cause mortality in a CAD diagnosis-free older population. We also estimated classification gains on adding the variant to the Framingham Risk Score (FRS) for CAD.

Methods and results: DNA was from an Established Populations for Epidemiological Study of the Elderly-Iowa cohort from 1988 (participants >71 years), with death certificates obtained to 2008 for 92% of participants. Cox regression models were adjusted for confounders and CAD risk factors. Of 1095 CAD diagnosis-free participants, 52% were heterozygous (CG) and 22% were homozygous (CC) for the risk C allele rs1333049. Unadjusted CAD-attributed death rates in the CC group were 30 vs 22 per 1000 person-years for the GG group. The C allele was associated with all-cause (hazard ratio, 1.19; 95% CI, 1.08-1.30) and CAD (hazard ratio, 1.29; 95% CI, 1.08-1.56) mortality, independent of CAD risk factors. There was no association with stroke deaths. Variant associations with CAD mortality were attenuated after the age of 80 years (age-interaction term P=0.05). In age group 71 to 80 years, FRS classified as high risk 21% of respondents who died of CAD within 10 years; adding 9p21 identified 27% of respondents.

Conclusions: In 71- to 80-year-old subjects free of CAD diagnoses, 9p21 is associated with excess mortality, mainly attributed to CAD mortality. Adding 9p21 to the FRS may improve the targeting of CAD prevention in older people, but validation in independent samples is needed for confirmation.

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Figures

Figure 1
Figure 1
Kaplan–Meier survival estimation (for coronary artery disease [CAD]–specific mortality) across genotypes of rs1333049 in different age groups.
Figure 2
Figure 2
Age group–specific hazard ratio (HR) per C allele of rs1333049.
See this image and copyright information in PMC

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