TY - JOUR
T1 - Aromatase gene polymorphisms are associated with survival among patients with cardiovascular disease in a sex-specific manner
AU - Beitelshees, Amber L.
AU - Johnson, Julie A.
AU - Hames, Megan L.
AU - Gong, Yan
AU - Cooper-Dehoff, Rhonda M.
AU - Wu, Jun
AU - Cresci, Sharon
AU - Ma, Cynthia X.
AU - Pepine, Carl J.
AU - Province, Michael A.
AU - Spertus, John A.
AU - McLeod, Howard L.
N1 - Funding Information:
Drs. Johnson, Pepine, and Cooper-DeHoff received grant funding from Abbott Laboratories. Drs. Cooper-DeHoff and Pepine along with the University of Florida hold U.S. Patent No. 5,991,731 related to INVEST. Dr. Pepine has been a consultant for Abbott Laboratories. These interests do not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.
PY - 2010
Y1 - 2010
N2 - Introduction: CYP19A1 encodes aromatase, the enzyme responsible for the conversion of androgens to estrogens, and may play a role in variation in outcomes among men and women with cardiovascular disease. We sought to examine genetic variation in CYP19A1 for its potential role in sex differences in cardiovascular disease outcomes. Methods: Caucasian individuals from two independent populations were assessed: 1) a prospective cohort of patients with acute coronary syndromes with 3-year mortality follow-up (n = 568) and 2) a nested case-control study from a randomized, controlled trial of hypertension patients with stable coronary disease in which the primary outcome was death, nonfatal myocardial infarction (MI) or nonfatal stroke (n = 619). Six CYP19A1 SNPs were genotyped (-81371 C>T, -45965 G>C, M201T, R264C, 80 A>G, and +32226 G>A). The sex*genotype interaction term was assessed for the primary outcome and compared by genotype in men and women when a significant interaction term was identified. Results: We identified a significant interaction between -81371 C>T and sex (p = 0.025) in the ACS population. The variant allele was associated with a 78% increase in mortality in men (HR 1.78, 95% confidence interval [CI] 1.08-2.94) and a nonsignificant 42% decrease in mortality among women (HR 0.58, 95% CI 0.22-1.54). We identified a similar association in the hypertensive CAD group, the -81371 C>T*sex interaction term was p<0.0001, with an associated 65% increase in death, MI, or stroke (HR 1.65, 95% CI 1.00-2.73) in men and a 69% decrease (HR 0.31, 95% CI 0.16-0.6) in women. Conclusions: Using two independent populations, this study is the first to document a significant interaction between CYP19A1 genotype and sex on cardiovascular outcomes. These findings could illuminate potential mechanisms of sex differences in cardiovascular disease outcomes.
AB - Introduction: CYP19A1 encodes aromatase, the enzyme responsible for the conversion of androgens to estrogens, and may play a role in variation in outcomes among men and women with cardiovascular disease. We sought to examine genetic variation in CYP19A1 for its potential role in sex differences in cardiovascular disease outcomes. Methods: Caucasian individuals from two independent populations were assessed: 1) a prospective cohort of patients with acute coronary syndromes with 3-year mortality follow-up (n = 568) and 2) a nested case-control study from a randomized, controlled trial of hypertension patients with stable coronary disease in which the primary outcome was death, nonfatal myocardial infarction (MI) or nonfatal stroke (n = 619). Six CYP19A1 SNPs were genotyped (-81371 C>T, -45965 G>C, M201T, R264C, 80 A>G, and +32226 G>A). The sex*genotype interaction term was assessed for the primary outcome and compared by genotype in men and women when a significant interaction term was identified. Results: We identified a significant interaction between -81371 C>T and sex (p = 0.025) in the ACS population. The variant allele was associated with a 78% increase in mortality in men (HR 1.78, 95% confidence interval [CI] 1.08-2.94) and a nonsignificant 42% decrease in mortality among women (HR 0.58, 95% CI 0.22-1.54). We identified a similar association in the hypertensive CAD group, the -81371 C>T*sex interaction term was p<0.0001, with an associated 65% increase in death, MI, or stroke (HR 1.65, 95% CI 1.00-2.73) in men and a 69% decrease (HR 0.31, 95% CI 0.16-0.6) in women. Conclusions: Using two independent populations, this study is the first to document a significant interaction between CYP19A1 genotype and sex on cardiovascular outcomes. These findings could illuminate potential mechanisms of sex differences in cardiovascular disease outcomes.
UR - http://www.scopus.com/inward/record.url?scp=78650739680&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0015180
DO - 10.1371/journal.pone.0015180
M3 - Article
C2 - 21170323
AN - SCOPUS:78650739680
SN - 1932-6203
VL - 5
SP - 1
EP - 6
JO - PloS one
JF - PloS one
IS - 12
M1 - e15180
ER -