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Effect of 9p21 genetic variation on coronary heart disease is not modified by other risk markers. The Atherosclerosis Risk in Communities (ARIC) Study.

TitleEffect of 9p21 genetic variation on coronary heart disease is not modified by other risk markers. The Atherosclerosis Risk in Communities (ARIC) Study.
Publication TypeJournal Article
Year of Publication2012
AuthorsFolsom AR, Nambi V, Pankow JS, Tang W, Farbakhsh K, Yamagishi K
Secondary AuthorsBoerwinkle E
JournalAtherosclerosis
Volume224
Issue2
Pagination435-9
Date Published2012 Oct
ISSN1879-1484
KeywordsBiomarkers, Chromosomes, Human, Pair 9, Coronary Artery Disease, European Continental Ancestry Group, Female, Gene Frequency, Gene-Environment Interaction, Genetic Predisposition to Disease, Humans, Incidence, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, United States
Abstract

OBJECTIVE: To determine whether the 9p21 SNP association with coronary heart disease is modified by other classical or novel risk markers.

METHODS: The 9p21 SNP (rs10757274) and multiple risk markers were measured in the Atherosclerosis Risk in Communities Study, and incident coronary disease events were ascertained. Effect modification (interaction) of the 9p21 SNP with risk markers was tested in Cox proportional hazard regression models.

RESULTS: The incidence rates of coronary heart disease per 1000 person-years were 14.4, 17.0, and 18.7 for AA, AG, and GG genotypes, yielding hazard ratios of 1.0, 1.20 (95% CI = 1.07-1.36), and 1.34 (95% CI = 1.16-1.53). There was no meaningful evidence of an interaction (all p-interaction > 0.04) between 9p21 SNP and any of 14 other risk markers for coronary heart disease. These included novel markers not previously explored for 9p21 interaction (e.g., cardiac troponin T and N-terminal pro-brain natriuretic peptide).

CONCLUSION: Our study extends evidence that the 9p21 SNP association with coronary heart disease is not modified by classical or novel risk markers. Our findings therefore rule out additional plausible pathways by which 9p21 might have increased coronary heart disease risk.

DOI10.1016/j.atherosclerosis.2012.08.007
Alternate JournalAtherosclerosis
PubMed ID22935634
PubMed Central IDPMC3459136
Grant ListHHSN2682011000-09C / / PHS HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100010C / / PHS HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268-201100012C / / PHS HHS / United States
HHSN268201100006C / / PHS HHS / United States