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Previous Volume 346:967-974 March 28, 2002 Number 13 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Krauss, R. M. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Sequence variants in the gene encoding estrogen receptor (ER-) may modify the effects of hormone-replacement therapy on levels of high-density lipoprotein (HDL) cholesterol and other outcomes related to estrogen treatment in postmenopausal women.

Methods We characterized 309 women with coronary artery disease who were enrolled in the Estrogen Replacement and Atherosclerosis trial with respect to eight previously described and two newly identified ER- polymorphisms, and we examined the association between these polymorphisms and the response of HDL cholesterol and other lipids to treatment with estrogen alone or estrogen plus progestin.

Results After adjustment for age, race, diabetes status, body-mass index, smoking status, alcohol intake, and frequency of exercise, the 18.9 percent of the women who had the IVS1–401 C/C genotype (i.e., with C on both chromosomes in intervening sequence 1 at position 401 before exon 2) had an increase in the HDL cholesterol level with hormone-replacement therapy that was more than twice the increase observed in the other women (13.1 mg per deciliter vs. 6.0 mg per deciliter, P for treatment-by-genotype interaction = 0.004); this effect was limited to changes in the HDL subfraction 3 (HDL₃) (P for interaction=0.04). Similar patterns of response were observed for three other highly linked ER- intron 1 polymorphisms close to the IVS1–401 site (range of P values for interaction = 0.07 to 0.005). The pattern of increased response of HDL cholesterol in women with the IVS1–401 C/C genotype was evident in both the women receiving estrogen and those receiving estrogen plus progestin, was preserved across racial and ethnic groups, and was significant among women who were compliant with the study medication (P<0.001).

Conclusions Postmenopausal women with coronary disease who have the ER- IVS1–401 C/C genotype, or several other closely related genotypes, have an augmented response of HDL cholesterol to hormone-replacement therapy.

Source Information

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 (D.M.R., J.X.) and the Hypertension and Vascular Disease Center (K.B.B.), Wake Forest University School of Medicine, Winston-Salem, N.C.

Address reprint requests to Dr. Herrington at Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1045.

Full Text of this Article

Related Letters:

Estrogen-Receptor Polymorphism and Hormone-Replacement Therapy
Garrido J. A., Grant E. C.G., Herrington D. M., Reboussin D. M.
Extract | Full Text | PDF  
N Engl J Med 2002; 347:762-763, Sep 5, 2002. Correspondence

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