Association of Estrogen Receptor β Gene Polymorphisms With Left Ventricular Mass and Wall Thickness in Women

• Published in: American journal of hypertension Vol. 18; no. 11; pp. 1388 - 1395
• Main Authors: Peter, Inga, Shearman, Amanda M., Vasan, Ramachandran S., Zucker, Deborah R., Schmid, Christopher H., Demissie, Serkalem, Cupples, L. Adrienne, Kuvin, Jeffrey T., Karas, Richard H., Mendelsohn, Michael E., Housman, David E., Benjamin, Emelia J.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-11-2005; Oxford University Press; Elsevier Science
• Subjects: Aged; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Echocardiography; Estrogen Receptor beta - genetics; estrogen receptors; Female; Gene Frequency; Genotype; Heart Ventricles - metabolism; Heart Ventricles - pathology; Hormones. Endocrine system; Humans; hypertension; Hypertension - complications; Hypertension - genetics; Hypertension - pathology; Hypertrophy, Left Ventricular - complications; Hypertrophy, Left Ventricular - genetics; Hypertrophy, Left Ventricular - pathology; Left ventricular hypertrophy; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Polymorphism, Single Nucleotide; polymorphisms (genetics); Regression Analysis; Sex Factors; polymorphisms (genetics); estrogen receptors; hypertension; Left ventricular hypertrophy; echocardiography; Human; Hypertension; Echocardiography; Cardiovascular disease; Wall thickness; Left ventricle; Polymorphism; Hormonal receptor
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/j.amjhyper.2005.05.023

Left ventricular (LV) hypertrophy is a significant risk factor for cardiovascular disease. Given sex-based differences in cardiac structure and remodeling, we hypothesized that variation in estrogen pathway genes might be associated with alteration of LV structure.
We studied 1249 unrelated individuals, 547 men and 702 women (mean age 59 years) from the Framingham Heart Study. Eight single nucleotide polymorphisms in the genes for estrogen receptor α and estrogen receptor β (
ESR2) were tested for association with 5 LV measures: LV mass (LVM), LV wall thickness (LVWT), LV internal diameter at end-diastole and end-systole, and fractional shortening. Sex-specific multiple regression analyses were performed adjusting for age, weight, height, systolic and diastolic blood pressure, hypertension treatment, diabetes, and in women, menopausal status.
In men, there was no evidence of association between the estrogen pathway polymorphisms tested and LV structure or function. In women, however, two polymorphisms,
ESR2 rs1256031 and
ESR2 rs1256059, in linkage disequilibrium with one another, were associated with LVM and LVWT (
P = .0007 to .03); the association was most pronounced in those women with hypertension (
P = .0006 to .01). The association did not appear to be explained by variation in blood pressure, plasma lipoprotein levels, or hyperglycemia.
The
ESR2 polymorphisms are associated with LV structural differences in women with hypertension in a community-based population. These data are consistent with the hypothesis that genetic factors may mediate part of the observed sex-based differences in LV structure and remodeling.