Variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in the Framingham Heart Study.
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.
Peter
Inga
I
Biostatistics Research Center, Institute for Clinical Research and Health Policy Studies, Massachusetts Institute of Technology, Cambridge, MA, USA. ipeter@tufts-nemc.org
Shearman
Amanda M
AM
Zucker
Deborah R
DR
Schmid
Christopher H
CH
Demissie
Serkalem
S
Cupples
L Adrienne
LA
Larson
Martin G
MG
Vasan
Ramachandran S
RS
D'Agostino
Ralph B
RB
Karas
Richard H
RH
Mendelsohn
Michael E
ME
Housman
David E
DE
Levy
Daniel
D
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
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