title: Variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in the Framingham Heart Study.
abstract: OBJECTIVE
  To examine the association between variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in men and women.
  
  
  METHODS
  In 1780 unrelated members of the community-based Framingham Heart Study offspring cohort, systolic blood pressure and diastolic blood pressure were measured over a total of six examination cycles encompassing 24 years of follow-up. Multivariate regression analyses were used to assess the relation between untreated cross-sectional and longitudinal blood pressure and polymorphisms at the estrogen receptor-alpha (ESR1), estrogen receptor-beta (ESR2), aromatase (CYP19A1), and nuclear receptor coactivator 1 (NCOA1) genes after adjustment for common risk factors.
  
  
  RESULTS
  In men, systolic blood pressure and pulse pressure (systolic blood pressure minus diastolic blood pressure) were associated with two polymorphisms in ESR1, while pulse pressure was also associated with variations in NCOA1 and CYP19A1. Polymorphisms in ESR1, CYP19A1, and NCOA1 were associated with diastolic blood pressure in women.
  
  
  CONCLUSIONS
  Although the underlying relations between genes involved in estrogen action and hypertension remain to be completely understood, our findings provide suggestive evidence of gender-specific contributions of estrogen-related genes to blood pressure variation. As no correction for multiple testing was performed in the analyses, we view these results as suggestive and not definitive. Further studies are warranted to confirm these results using a comprehensive set of polymorphisms in order to shed more light on the involvement of estrogen in blood pressure regulation.
authors.affiliation: Biostatistics Research Center, Institute for Clinical Research and Health Policy Studies, Massachusetts Institute of Technology, Cambridge, MA, 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: 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: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
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: Daniel
authors.initials: D
authors.lastname: Levy
mesh_terms: D001141:Aromatase / Q000235:genetics; D001483:Base Sequence; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics; D004967:Estrogens / Q000235:genetics* / Q000502:physiology; D005260:Female; D051548:Histone Acetyltransferases; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D008404:Massachusetts; D008875:Middle Aged; D015999:Multivariate Analysis; D056920:Nuclear Receptor Coactivator 1; D011110:Polymorphism, Genetic; D012727:Sex Characteristics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D014157:Transcription Factors; D004247:DNA; D001141:Aromatase; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1