Author Affiliations: Department of Cardiovascular Genetics, University of Utah, Salt Lake City).
The article by Shearman et al1 in this
issue of THE JOURNAL brings intriguing genetic data to bear on several issues
of considerable current controversy—the relationship between coronary
artery disease (CAD) and estrogen action, the general utility of CAD associations
with variants in candidate genes, and the challenges of identifying causative
gene variants for common disease. In this interesting hybrid of a case-control
and prospective design, the investigators extracted DNA from blood samples
of a subset of unrelated members of the Framingham offspring cohort who were
alive at examination 6 (approximately 27 years after the baseline examination).
The subset was selected to achieve an approximately equal number of representative
men and women from the cohort. The effects of several estrogen receptor α
(ESR1) gene variants were tested using primarily
a case-control analysis in which offspring who had developed atherosclerotic
disease by the sixth examination were considered cases and the remainder controls.
A 3.0-fold increase in risk of myocardial infarction (MI) (P<.001) was associated with the CC genotype
of the ESR1 c.454-397T>C variant (compared with the TT and CT genotypes combined)
after correction for multiple risk factors. Lower odds ratios were associated
with broader end points. Virtually identical results were obtained when data
were analyzed as a prospective survival study.
Hopkins PN, Brinton EA. Estrogen Receptor 1 Variants and Coronary Artery Disease: Shedding Light Into a Murky Pool. JAMA. 2003;290(17):2317–2319. doi:https://doi.org/10.1001/jama.290.17.2317
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