XbaI polymorphism of ESR1 gene might influence the effect of raloxifene on the endothelial function
Andrej Zavratnik1, Branka Žegura1, Martin Rakuša1, Janja Marc2, Janez Preželj3 & Marija Pfeifer3
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.