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Association of candidate gene variation with baseline coronary arterial calcification (CAC) in asymptomatic women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS)
Author(s) -
Miller Virginia M,
Petterson Tanya M,
Jeavons Elysia N,
Heit John A,
Andrade Mariza
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.793.19
To test candidate gene variation for an association with atherosclerosis, DNA from 714 women participating in KEEPS (a clinical trial of early menopause hormonal therapy to prevent atherosclerosis) was genotyped for 13,229 single nucleotide polymorphisms (SNPs) within 769 anticoagulant, procoagulant, fibrinolytic or innate immunity pathway genes. 75 samples were removed due to genotype call rate<0.95, relatedness or duplication; 18 were CEPH controls. 1275 SNPs were removed for quality control; 504 were ancestry informative markers (AIM). We tested the remaining SNPs for an association with CAC (CAC score=0 vs. >0) using logistic regression with an additive effect, adjusting for % Caucasian ancestry using AIM, cardiovascular risk factors, and menopausal symptom score. 82 women had a baseline CAC score >0–50 Agatston Units. IRAK2 rs11465886 (odds ratio [OR]=4.36, p=6.5E‐05) and ABO rs630014 (OR=0.49, p=9.04E‐05) were associated with CAC. IRAK2 encodes for innate immunity and intracellular signaling cascade proteins, while ABO encodes for a glycosyltransferase involved with post‐translational procoagulant protein modification. (Funded by grants from the Aurora Foundation and NHLBI HL78638).