title: Association of estrogen receptor beta gene polymorphisms with left ventricular mass and wall thickness in women.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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 alpha and estrogen receptor beta (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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biostatistics Research Center, Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA. ipeter@tufts-nemc.org
authors.forename: Inga
authors.initials: I
authors.lastname: Peter
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Shearman
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Zucker
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Schmid
authors.forename: Serkalem
authors.initials: S
authors.lastname: Demissie
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Kuvin
authors.forename: Richard H
authors.initials: RH
authors.lastname: Karas
authors.forename: Michael E
authors.initials: ME
authors.lastname: Mendelsohn
authors.forename: David E
authors.initials: DE
authors.lastname: Housman
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
mesh_terms: D000368:Aged; D004452:Echocardiography; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012737:Sex Factors
chemical_list: D047629:Estrogen Receptor beta