Objectives: The selective estrogen receptor modulator, raloxifene, exerts a part of its actions through the estrogen receptor alpha activation. We explored if polymorphisms of ESR1 gene modify the effects of 6 months raloxifene treatment on endothelial function.
Methods: Two intronic (PvuII and XbaI), and one exonic polymorphism (P325P) of ESR1 were analyzed in 53 postmenopausal women, mean age 59.7+6.2. The flow mediated endothelium dependent vasodilation (FMD) and cell adhesion molecules (CAM) ICAM-1, VCAM-1 and E-selectin, were measured before and after 6 months of raloxifene treatment. SSCP method was used to determine the P325P and RFLP to determine XbaI and PvuII polymorphisms.
Results: There was no relation between ESR1 genotypes and either FMD or CAM levels, at baseline. After 6 months of raloxifene treatment, the FMD was significantly greater in subjects with XX genotype of XbaI polymorphism compared to xx, and of borderline significance compared to Xx genotype (P=0.03 and P=0.053, respectively). Neither the PvuII nor P325P ESR1 gene polymorphisms influenced the FMD after 6 months of treatment. None of the ESR1 gene polymorphisms influenced the levels of CAM. When analysing the whole group, a significant decrease in E-selectin and a significant increase in ICAM-1 levels, independently of genotypes was observed (P<0.001 and P=0.029, respectively), but no influence on VCAM-1 level and FMD, was found.
Conclusion: Our data suggest that XbaI polymorphism of ESR1 gene might influence the beneficial effect of raloxifene treatment on endothelial function. This effect could be of significant farmacogenomic and clinical importance.
03 - 07 May 2008
European Society of Endocrinology