1. The Association of Estrogen Receptor-β Gene Variation With Salt-Sensitive Blood Pressure
- Author
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Willa A. Hsueh, Yii-Der Ida Chen, Jessica Lasky-Su, Bei Sun, Worapaka Manosroi, Luminita H. Pojoga, Thomas A. Buchanan, Jinrui Cui, Jonathan S. Williams, Anny H. Xiang, Chevon M. Rariy, Gordon H. Williams, Ellen W. Seely, Kent D. Taylor, Aditi R. Saxena, Xiuqing Guo, Jerome I. Rotter, Leslie J. Raffel, Mark O. Goodarzi, and Jia Wei Tan
- Subjects
0301 basic medicine ,Male ,Aging ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Estrogen receptor ,Blood Pressure ,030204 cardiovascular system & hematology ,Sodium Chloride ,Cardiovascular ,Biochemistry ,0302 clinical medicine ,Endocrinology ,Risk Factors ,Age Factors ,Single Nucleotide ,Middle Aged ,Menopause ,Hypertension ,Female ,Adult ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Clinical Sciences ,Dietary ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Paediatrics and Reproductive Medicine ,03 medical and health sciences ,Young Adult ,Endocrinology & Metabolism ,Sex Factors ,Clinical Research ,Internal medicine ,medicine ,Genetics ,Humans ,Estrogen Receptor beta ,Genetic Predisposition to Disease ,Sodium Chloride, Dietary ,Allele ,Polymorphism ,Clinical Research Articles ,Estrogen receptor beta ,Genetic Association Studies ,Aged ,business.industry ,Contraception/Reproduction ,Biochemistry (medical) ,medicine.disease ,Estrogen ,030104 developmental biology ,Blood pressure ,business ,Estrogen receptor alpha - Abstract
Author(s): Manosroi, Worapaka; Tan, Jia Wei; Rariy, Chevon M; Sun, Bei; Goodarzi, Mark O; Saxena, Aditi R; Williams, Jonathan S; Pojoga, Luminita H; Lasky-Su, Jessica; Cui, Jinrui; Guo, Xiuqing; Taylor, Kent D; Chen, Yii-Der I; Xiang, Anny H; Hsueh, Willa A; Raffel, Leslie J; Buchanan, Thomas A; Rotter, Jerome I; Williams, Gordon H; Seely, Ellen W | Abstract: ContextHypertension in young women is uncommon compared with young men and older women. Estrogen appears to protect most women against hypertension, with incidence increasing after menopause. Because some premenopausal women develop hypertension, estrogen may play a different role in these women. Genetic variations in the estrogen receptor (ER) are associated with cardiovascular disease. ER-β, encoded by ESR2, is the ER predominantly expressed in vascular smooth muscle.ObjectiveTo determine an association of single nucleotide polymorphisms in ESR2 with salt sensitivity of blood pressure (SSBP) and estrogen status in women.MethodsCandidate gene association study with ESR2 and SSBP conducted in normotensive and hypertensive women and men in two cohorts: International Hypertensive Pathotype (HyperPATH) (n = 584) (discovery) and Mexican American Hypertension-Insulin Resistance Study (n = 662) (validation). Single nucleotide polymorphisms in ESR1 (ER-α) were also analyzed. Analysis conducted in younger (l51 years, premenopausal, "estrogen-replete") and older women (≥51 years, postmenopausal, "estrogen-deplete"). Men were analyzed to control for aging.ResultsMultivariate analyses of HyperPATH data between variants of ESR2 and SSBP documented that ESR2 rs10144225 minor (risk) allele carriers had a significantly positive association with SSBP driven by estrogen-replete women (β = +4.4 mm Hg per risk allele, P = 0.004). Findings were confirmed in Hypertension Insulin-Resistance Study premenopausal women. HyperPATH cohort analyses revealed risk allele carriers vs noncarriers had increased aldosterone/renin ratios. No associations were detected with ESR1.ConclusionsThe variation at rs10144225 in ESR2 was associated with SSBP in premenopausal women (estrogen-replete) and not in men or postmenopausal women (estrogen-deplete). Inappropriate aldosterone levels on a liberal salt diet may mediate the SSBP.
- Published
- 2017