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(Hypertension. 2007;49:1000.)
© 2007 American Heart Association, Inc.

Original Articles

Age-Related Changes in Echocardiographic Measurements

Association With Variation in the Estrogen Receptor- Gene

Inga Peter; Gordon S. Huggins; Amanda M. Shearman; Arthur Pollak; Christopher H. Schmid; L. Adrienne Cupples; Serkalem Demissie; Richard D. Patten; Richard H. Karas; David E. Housman; Michael E. Mendelsohn; Ramachandran S. Vasan; Emelia J. Benjamin

From the Institute for Clinical Research and Health Policy Studies (I.P., C.H.S.) and Molecular Cardiology Research Institute (G.S.H., R.D.P., R.H.K., M.E.M.), Tufts-New England Medical Center, Boston, Mass; the Center for Cancer Research (A.M.S., D.E.H.), Massachusetts Institute of Technology, Cambridge; National Heart, Lung, and Blood Institute’s Framingham Heart Study (R.S.V., E.J.B.), Framingham, Mass; the Biostatistics Department (L.A.C., S.D.), Boston University School of Public Health, Mass; the Department of Preventive Medicine and Cardiology (R.S.V., E.J.B.), Boston University School of Medicine, Mass; and the Cardiology Department (A.P.), Hadassah–Hebrew University Medical Center, Jerusalem, Israel.

Correspondence to Inga Peter, Tufts-New England Medical Center, 750 Washington St, NEMC #63, Boston, MA 02111; e-mail ipeter{at}tufts-nemc.org

Left ventricular (LV) mass and other LV measures have been shown to be heritable. In this study we hypothesized that functional variation in the gene coding for estrogen receptor- (ESR1), known for mediating the effect of estrogens on myocardium, is associated with age-related changes in LV structure. Four genetic markers (ESR1 TA repeat; rs2077647, or +30T>C; rs2234693, or PvuII; and rs9340799, or XbaI) were genotyped in 847 unrelated individuals (488 women) from the Framingham Offspring Study, who attended 2 examination cycles 16 years apart (mean ages at first examination: 43±9 years; at follow-up: 59±9 years). ANCOVA was used to assess the association of polymorphisms and their haplotypes with cross-sectional measurements and longitudinal changes in LV mass, wall thickness, end-diastolic and end-systolic internal diameter, and fractional shortening after adjustment for factors known to influence these variables. Changes over time were detected for all of the LV measurements (P ranging from <0.0001 to 0.02), except for fractional shortening in men. The SS genotype of the ESR1 TA repeat polymorphism in the promoter region was associated with longitudinal changes in LV mass and LV wall thickness (P ranging from 0.0006 to 0.01). Moreover, the TA[S]–+30[T]–PvuII[T]–XbaI[A] haplotype (frequency: 47.5%) was associated with greater LV changes as compared with the TA[L]–+30[C]–PvuII[C]–XbaI[G] haplotype (frequency: 31.8%). Our results are consistent with the hypothesis that common ESR1 polymorphisms are significantly associated with age-related changes in LV structure. Understanding the mechanisms predisposing to unfavorable LV remodeling of the heart with advancing age may aid in the discovery of new therapeutic targets for the prevention of heart failure.

Key Words: echocardiography • left ventricular remodeling • estrogen receptor- • restriction fragment length • single nucleotide polymorphism

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