Maturitas
Volume 67, Issue 1 , Pages 84-90, September 2010

XbaI polymorphism of the estrogen receptor alpha gene influences the effect of raloxifene on the endothelial function

  • Andrej Zavratnik

      Affiliations

    • Department of Endocrinology, University Medical Centre, Ljubljanska 5, 2000 Maribor, Slovenia
    • Corresponding Author InformationCorresponding author. Tel.: +386 2 321 23 36; fax: +386 2 331 23 93.
    • ,
  • Branka Žegura

      Affiliations

    • Clinic of gynecology and obstetrics, University Medical Centre, Ljubljanska 5, 2000 Maribor, Slovenia
    • ,
  • Janja Marc

      Affiliations

    • Department of Biochemistry, Faculty of Pharmacy, Aškrčeva 7, 1000 Ljubljana, Slovenia
    • ,
  • Janez Preželj

      Affiliations

    • Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre, Zaloška 7, 1525 Ljubljana, Slovenia
    • ,
  • Marija Pfeifer

      Affiliations

    • Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre, Zaloška 7, 1525 Ljubljana, Slovenia

Received 19 January 2010; received in revised form 27 May 2010; accepted 28 May 2010. published online 14 June 2010.

Abstract 

Objectives

Cardiovascular disease is the leading cause of death in postmenopausal women and estrogen deficiency may be an important factor in its development. The selective estrogen receptor modulator, raloxifene, exerts a part of its actions through the estrogen receptor alpha (ESR1) activation. We explored if polymorphisms of the ESR1 modify the effects of 6 months raloxifene treatment on endothelial function.

Methods

A total of 53 postmenopausal women, mean age 59.7±6.2, finished the prospective clinical trial. The PvuII, XbaI, and P325P polymorphisms of the ESR1 gene were analyzed. In all subjects endothelium-dependent flow mediated dilatation (FMD) and cell adhesion molecules (CAM) ICAM-1, VCAM-1 and E-selectin were measured before and after 6 months of raloxifene treatment.

Results

There was no difference in FMD between the ESR1 genotypes, at baseline. After raloxifene treatment, the FMD was significantly greater in subjects with XX genotype of XbaI polymorphism compared to xx (p=0.03) and borderline greater when compared to Xx genotype (p=0.053). The FMD increased significantly with raloxifene treatment in women with Xx genotype of XbaI and Pp genotype of PvuII polymorphisms (p=0.027 and p=0.034, respectively). The P325P polymorphism did not influence the FMD after raloxifene. None of the ESR1 gene polymorphisms had any impact on the levels of CAM before or after the treatment. When analysing the whole group, a significant decrease in E-selectin (p<0.001) and a small increase in ICAM-1 levels (p=0.029) was observed with raloxifene treatment, but no influence on VCAM-1 levels or FMD overall was seen.

Conclusion

Our data suggest that XbaI and possibly PvuII polymorphisms of the ESR1 gene influence the impact of raloxifene treatment on endothelial function. This effect could be of pharmacogenomic and clinical importance.

Keywords: ESR1 polymorphisms, Raloxifene, Endothelium-dependent vasodilatation, Cell adhesion molecules, Postmenopausal women

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PII: S0378-5122(10)00220-3

doi:10.1016/j.maturitas.2010.05.011

Maturitas
Volume 67, Issue 1 , Pages 84-90, September 2010

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