Polymorphisms and Haplotypes of the Estrogen Receptor-β Gene (ESR2) and Cardiovascular Disease in Men and Women

Background: Cohort studies suggest an association between variation in the estrogen receptor-α gene (ESR1) and cardiovascular disease (CVD), but data are lacking for the effect of variation in the estrogen receptor-β gene (ESR2). Methods: Three polymorphisms of the ESR2 gene, and their associated ha...

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Vydané v:	Clinical chemistry (Baltimore, Md.) Ročník 53; číslo 10; s. 1749 - 1756
Hlavní autori:	Rexrode, Kathryn M, Ridker, Paul M, Hegener, Hillary H, Buring, Julie E, Manson, JoAnn E, Zee, Robert YL
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Washington, DC American Association for Clinical Chemistry 01.10.2007
Predmet:	Adult Aged Aged, 80 and over Analytical, structural and metabolic biochemistry Biological and medical sciences Brain Ischemia - complications Cardiovascular Diseases - etiology Cardiovascular Diseases - genetics Case-Control Studies Cohort Studies Estrogen Receptor beta - genetics Female Fundamental and applied biological sciences. Psychology Haplotypes Humans Investigative techniques, diagnostic techniques (general aspects) Male Medical sciences Middle Aged Myocardial Infarction - genetics Polymorphism, Genetic Promoter Regions, Genetic Risk Sex Factors Stroke - etiology Stroke - genetics White People Estrogen receptor β Genetic variability Gene Clinical biology Sex Cardiovascular disease Genotype Genetics Biochemistry Molecular biology Haplotype Polymorphism
ISSN:	0009-9147, 1530-8561
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Abstract	Background: Cohort studies suggest an association between variation in the estrogen receptor-α gene (ESR1) and cardiovascular disease (CVD), but data are lacking for the effect of variation in the estrogen receptor-β gene (ESR2). Methods: Three polymorphisms of the ESR2 gene, and their associated haplotypes, were evaluated in 296 white women from the Women’s Health Study and 566 white men from the Physicians’ Health Study who developed CVD [myocardial infarction (MI) or ischemic stroke], each matched 1:1 to a member of the cohort study who remained free from CVD. Blood samples and cardiovascular risk information were collected at baseline. Results: Women, but not men, who developed CVD or MI, but not ischemic stroke, were more likely to have the rs1271572 polymorphism variant T allele (P = 0.05 and 0.02) and less likely to have the rs1256049 polymorphism variant A allele (P = 0.003 and 0.004). No associations were observed for rs4986938. In conditional logistic multivariate regression, the rs1271572 variant was associated with increased odds of CVD [odds ratio (OR) = 1.49, 95% CI: 1.10–2.01] and MI (OR = 1.46, 95% CI: 0.96–2.23), whereas the rs1256049 variant was associated with decreased odds of CVD (OR = 0.37, 95% CI: 0.17–0.79) and MI (OR = 0.25, 95% CI: 0.09–0.73) in women. A common haplotype that included the rs1271572 variant was associated with a 7-fold increased risk of MI in women. Conclusions: Two tightly linked polymorphisms of ESR2 were associated with risk of CVD, particularly MI, in women but not men. Additional studies of ESR2 genetic variation and risk of CVD are warranted.
AbstractList	Background: Cohort studies suggest an association between variation in the estrogen receptor-α gene (ESR1) and cardiovascular disease (CVD), but data are lacking for the effect of variation in the estrogen receptor-β gene (ESR2). Methods: Three polymorphisms of the ESR2 gene, and their associated haplotypes, were evaluated in 296 white women from the Women’s Health Study and 566 white men from the Physicians’ Health Study who developed CVD [myocardial infarction (MI) or ischemic stroke], each matched 1:1 to a member of the cohort study who remained free from CVD. Blood samples and cardiovascular risk information were collected at baseline. Results: Women, but not men, who developed CVD or MI, but not ischemic stroke, were more likely to have the rs1271572 polymorphism variant T allele (P = 0.05 and 0.02) and less likely to have the rs1256049 polymorphism variant A allele (P = 0.003 and 0.004). No associations were observed for rs4986938. In conditional logistic multivariate regression, the rs1271572 variant was associated with increased odds of CVD [odds ratio (OR) = 1.49, 95% CI: 1.10–2.01] and MI (OR = 1.46, 95% CI: 0.96–2.23), whereas the rs1256049 variant was associated with decreased odds of CVD (OR = 0.37, 95% CI: 0.17–0.79) and MI (OR = 0.25, 95% CI: 0.09–0.73) in women. A common haplotype that included the rs1271572 variant was associated with a 7-fold increased risk of MI in women. Conclusions: Two tightly linked polymorphisms of ESR2 were associated with risk of CVD, particularly MI, in women but not men. Additional studies of ESR2 genetic variation and risk of CVD are warranted. Cohort studies suggest an association between variation in the estrogen receptor-alpha gene (ESR1) and cardiovascular disease (CVD), but data are lacking for the effect of variation in the estrogen receptor-beta gene (ESR2). Three polymorphisms of the ESR2 gene, and their associated haplotypes, were evaluated in 296 white women from the Women's Health Study and 566 white men from the Physicians' Health Study who developed CVD [myocardial infarction (MI) or ischemic stroke], each matched 1:1 to a member of the cohort study who remained free from CVD. Blood samples and cardiovascular risk information were collected at baseline. Women, but not men, who developed CVD or MI, but not ischemic stroke, were more likely to have the rs1271572 polymorphism variant T allele (P = 0.05 and 0.02) and less likely to have the rs1256049 polymorphism variant A allele (P = 0.003 and 0.004). No associations were observed for rs4986938. In conditional logistic multivariate regression, the rs1271572 variant was associated with increased odds of CVD [odds ratio (OR) = 1.49, 95% CI: 1.10-2.01] and MI (OR = 1.46, 95% CI: 0.96-2.23), whereas the rs1256049 variant was associated with decreased odds of CVD (OR = 0.37, 95% CI: 0.17-0.79) and MI (OR = 0.25, 95% CI: 0.09-0.73) in women. A common haplotype that included the rs1271572 variant was associated with a 7-fold increased risk of MI in women. Two tightly linked polymorphisms of ESR2 were associated with risk of CVD, particularly MI, in women but not men. Additional studies of ESR2 genetic variation and risk of CVD are warranted. Cohort studies suggest an association between variation in the estrogen receptor-alpha gene (ESR1) and cardiovascular disease (CVD), but data are lacking for the effect of variation in the estrogen receptor-beta gene (ESR2).BACKGROUNDCohort studies suggest an association between variation in the estrogen receptor-alpha gene (ESR1) and cardiovascular disease (CVD), but data are lacking for the effect of variation in the estrogen receptor-beta gene (ESR2).Three polymorphisms of the ESR2 gene, and their associated haplotypes, were evaluated in 296 white women from the Women's Health Study and 566 white men from the Physicians' Health Study who developed CVD [myocardial infarction (MI) or ischemic stroke], each matched 1:1 to a member of the cohort study who remained free from CVD. Blood samples and cardiovascular risk information were collected at baseline.METHODSThree polymorphisms of the ESR2 gene, and their associated haplotypes, were evaluated in 296 white women from the Women's Health Study and 566 white men from the Physicians' Health Study who developed CVD [myocardial infarction (MI) or ischemic stroke], each matched 1:1 to a member of the cohort study who remained free from CVD. Blood samples and cardiovascular risk information were collected at baseline.Women, but not men, who developed CVD or MI, but not ischemic stroke, were more likely to have the rs1271572 polymorphism variant T allele (P = 0.05 and 0.02) and less likely to have the rs1256049 polymorphism variant A allele (P = 0.003 and 0.004). No associations were observed for rs4986938. In conditional logistic multivariate regression, the rs1271572 variant was associated with increased odds of CVD [odds ratio (OR) = 1.49, 95% CI: 1.10-2.01] and MI (OR = 1.46, 95% CI: 0.96-2.23), whereas the rs1256049 variant was associated with decreased odds of CVD (OR = 0.37, 95% CI: 0.17-0.79) and MI (OR = 0.25, 95% CI: 0.09-0.73) in women. A common haplotype that included the rs1271572 variant was associated with a 7-fold increased risk of MI in women.RESULTSWomen, but not men, who developed CVD or MI, but not ischemic stroke, were more likely to have the rs1271572 polymorphism variant T allele (P = 0.05 and 0.02) and less likely to have the rs1256049 polymorphism variant A allele (P = 0.003 and 0.004). No associations were observed for rs4986938. In conditional logistic multivariate regression, the rs1271572 variant was associated with increased odds of CVD [odds ratio (OR) = 1.49, 95% CI: 1.10-2.01] and MI (OR = 1.46, 95% CI: 0.96-2.23), whereas the rs1256049 variant was associated with decreased odds of CVD (OR = 0.37, 95% CI: 0.17-0.79) and MI (OR = 0.25, 95% CI: 0.09-0.73) in women. A common haplotype that included the rs1271572 variant was associated with a 7-fold increased risk of MI in women.Two tightly linked polymorphisms of ESR2 were associated with risk of CVD, particularly MI, in women but not men. Additional studies of ESR2 genetic variation and risk of CVD are warranted.CONCLUSIONSTwo tightly linked polymorphisms of ESR2 were associated with risk of CVD, particularly MI, in women but not men. Additional studies of ESR2 genetic variation and risk of CVD are warranted.
Author	Zee, Robert YL Rexrode, Kathryn M Manson, JoAnn E Hegener, Hillary H Buring, Julie E Ridker, Paul M
Author_xml	– sequence: 1 givenname: Kathryn M surname: Rexrode fullname: Rexrode, Kathryn M organization: Division of Preventive Medicine and the Center for Cardiovascular Disease Prevention – sequence: 2 givenname: Paul M surname: Ridker fullname: Ridker, Paul M organization: Division of Preventive Medicine and the Center for Cardiovascular Disease Prevention,, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA – sequence: 3 givenname: Hillary H surname: Hegener fullname: Hegener, Hillary H organization: Division of Preventive Medicine and the Center for Cardiovascular Disease Prevention,, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA – sequence: 4 givenname: Julie E surname: Buring fullname: Buring, Julie E organization: Division of Preventive Medicine and the Center for Cardiovascular Disease Prevention,, Department of Epidemiology, Harvard School of Public Health, Boston, MA, Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, MA – sequence: 5 givenname: JoAnn E surname: Manson fullname: Manson, JoAnn E organization: Division of Preventive Medicine and the Center for Cardiovascular Disease Prevention,, Department of Epidemiology, Harvard School of Public Health, Boston, MA – sequence: 6 givenname: Robert YL surname: Zee fullname: Zee, Robert YL organization: Division of Preventive Medicine and the Center for Cardiovascular Disease Prevention,, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
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Snippet	Background: Cohort studies suggest an association between variation in the estrogen receptor-α gene (ESR1) and cardiovascular disease (CVD), but data are... Cohort studies suggest an association between variation in the estrogen receptor-alpha gene (ESR1) and cardiovascular disease (CVD), but data are lacking for...
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SubjectTerms	Adult Aged Aged, 80 and over Analytical, structural and metabolic biochemistry Biological and medical sciences Brain Ischemia - complications Cardiovascular Diseases - etiology Cardiovascular Diseases - genetics Case-Control Studies Cohort Studies Estrogen Receptor beta - genetics Female Fundamental and applied biological sciences. Psychology Haplotypes Humans Investigative techniques, diagnostic techniques (general aspects) Male Medical sciences Middle Aged Myocardial Infarction - genetics Polymorphism, Genetic Promoter Regions, Genetic Risk Sex Factors Stroke - etiology Stroke - genetics White People
Title	Polymorphisms and Haplotypes of the Estrogen Receptor-β Gene (ESR2) and Cardiovascular Disease in Men and Women
URI	https://www.ncbi.nlm.nih.gov/pubmed/17702854 https://www.proquest.com/docview/68300175 https://pubmed.ncbi.nlm.nih.gov/PMC2085372
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