Pharmacogenomics of Estrogens on Changes in Carotid Artery Intima-medial Thickness and Coronary Arterial Calcification: Kronos Early Estrogen Prevention Study

Overview

Journal Physiol Genomics

Publisher American Physiological Society

Specialties Genetics
Molecular Biology

Date 2015 Oct 29

PMID 26508701

Citations 15

Authors

Virginia M Miller

Gregory D Jenkins

Joanna M Biernacka

John A Heit

Gordon S Huggins

Howard N Hodis

Matthew J Budoff

Rogerio A Lobo

Hugh S Taylor

JoAnn E Manson

Dennis M Black

Frederick Naftolin

S Mitchell Harman

Mariza de Andrade

Affiliations

Soon will be listed here.

Abstract

Prior to the initiation of menopausal hormone treatment (MHT), genetic variations in the innate immunity pathway were found to be associated with carotid artery intima-medial thickness (CIMT) and coronary arterial calcification (CAC) in women (n = 606) enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Whether MHT might affect these associations is unknown. The association of treatment outcomes with variation in the same 764 candidate genes was evaluated in the same KEEPS participants 4 yr after randomization to either oral conjugated equine estrogens (0.45 mg/day), transdermal 17β-estradiol (50 μg/day), each with progesterone (200 mg/day) for 12 days each month, or placebo pills and patch. Twenty SNPs within the innate immunity pathway most related with CIMT after 4 yr were not among those associated with CIMT prior to MHT. In 403 women who completed the study in their assigned treatment group, single nucleotide polymorphisms (SNPs) within the innate immunity pathway were found to alter the treatment effect on 4 yr change in CIMT (i.e., significant interaction between treatment and genetic variation in the innate immunity pathway; P < 0.001). No SNPs by treatment effects were observed with changes of CAC >5 Agatston units after 4 yr. Results of this study suggest that hormonal status may interact with genetic variants to influence cardiovascular phenotypes, specifically, the pharmacogenomic effects within the innate immunity pathway for CIMT.

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