Common estrogen receptor polymorphism augments effects of hormone replacement therapy on E-selectin but not C-reactive protein.

Published

Journal Article

BACKGROUND: The estrogen receptor-alpha (ER-alpha) IVS1-401 polymorphism identifies a group of women (approximately 20%) who have augmented effects of hormone replacement therapy (HRT) on levels of HDL cholesterol. This study sought to determine if this augmentation extends to HRT regulation of E-selectin and C-reactive protein (CRP) and to explore possible mechanisms by which this polymorphism might influence estrogen action. METHODS AND RESULTS: Serum levels of soluble E-selectin and CRP were measured at baseline and 1 year in 264 postmenopausal women randomized to treatment with oral conjugated equine estrogen (0.625 mg/d), estrogen plus progestin (medroxyprogesterone acetate 2.5 mg/d), or placebo. Women with the ER-alpha IVS1-401 C/C genotype receiving HRT had nearly a 2-fold greater reduction in E-selectin compared with C/T or T/T women (P for interaction=0.02). In contrast, there was no augmentation of the HRT-associated increase in CRP among the C/C women compared with C/T or T/T women (P for interaction=0.54). Of luciferase reporter constructs containing sequences spanning the IVS1-401 T/C polymorphism, expression of the construct containing the C allele was enhanced >10-fold, with cotransfection of a constitutively expressed B-myb vector. In contrast, B-myb resulted in only a 2.5-fold increase in expression of the T allele construct. CONCLUSIONS: Women with the ER-alpha IVS1-401 C/C genotype have greater reductions in E-selectin but no further increases in CRP with HRT. The C allele produces a functional binding site for the transcription factor B-myb. The impact of this polymorphism on ER-alpha transcription and other estrogen-sensitive intermediate and clinical end points has not yet been established.

Full Text

Duke Authors

Cited Authors

  • Herrington, DM; Howard, TD; Brosnihan, KB; McDonnell, DP; Li, X; Hawkins, GA; Reboussin, DM; Xu, J; Zheng, SL; Meyers, DA; Bleecker, ER

Published Date

  • April 23, 2002

Published In

Volume / Issue

  • 105 / 16

Start / End Page

  • 1879 - 1882

PubMed ID

  • 11997270

Pubmed Central ID

  • 11997270

Electronic International Standard Serial Number (EISSN)

  • 1524-4539

Digital Object Identifier (DOI)

  • 10.1161/01.cir.0000016173.98826.88

Language

  • eng

Conference Location

  • United States