Circulation. 2002;105:1879-1882
Published online before print April 8, 2002, doi: 10.1161/01.CIR.0000016173.98826.88
Published online before print April 8, 2002, doi: 10.1161/01.CIR.0000016173.98826.88
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(Circulation. 2002;105:1879.)
© 2002 American Heart Association, Inc.
Brief Rapid Communications |
Common Estrogen Receptor Polymorphism Augments Effects of Hormone Replacement Therapy on E-Selectin but Not C-Reactive Protein
From the Departments of Internal Medicine (D.M.H., G.A.H., E.R.B.), Pediatrics (T.D.H., S.L.Z., D.A.M.), and Public Health Sciences (J.X., D.M.R.), the Hypertension and Vascular Disease Center (K.B.B.), Wake Forest University School of Medicine, Winston-Salem; and the Department of Pharmacology and Cancer Biology (D.P.M., X.L.), Duke University Medical Center, Durham, NC.
Correspondence to David M. Herrington, MD, MHS, Department of Internal Medicine/Cardiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1045. E-mail kklein{at}wfubmc.edu
Background— The estrogen receptor-
(ER-) IVS1-401 polymorphism identifies a group of women (
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- 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- 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- transcription and other estrogen-sensitive intermediate and clinical end points has not yet been established.
Key Words: receptors • genetics • women • coronary disease
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