title: Exonic, but not intronic polymorphisms of ESR1 gene might influence the hypolipemic effect of raloxifene.
abstract: Studies have shown that selective modulator of estrogen receptor raloxifene, exerts hypolipemic properties at least partially through estrogen receptor alpha activation. To test the hypothesis that polymorphisms of estrogen receptor alpha are associated with the influence of 6 months raloxifene treatment on serum lipids, two intronic (PvuII and XbaI), and one exonic polymorphism (P325P) were analyzed in 49 postmenopausal women, mean age 62.5+/-5.7 years. In all subjects, the total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were determined before and after 6 months of raloxifene treatment. We were unable to find any relationship between estrogen receptor alpha genotype and serum lipids at baseline. At the end of 6 months treatment with raloxifene, the mean decrease of total cholesterol and LDL cholesterol, independently of genotypes, was highly significant, but no influence on HDL and triglycerides concentrations was found. Neither the PvuII nor XbaI ESR1 gene polymorphisms were associated with the magnitude of lipid changes after 6 months treatment, whereas the subjects with non-CC genotype of P325P mutation had significantly lower total cholesterol and LDL cholesterol concentrations, and higher decline of total cholesterol (p<0.05).
  
  
  CONCLUSIONS
  Our data suggest that exonic, but not intronic polymorphisms of estrogen receptor alpha gene might intensify the cholesterol lowering effect of raloxifene.
authors.affiliation: Department of Endocrinology and Diabetology, Teaching Hospital Maribor, Ljubljanska 5, 2000 Maribor, Slovenia. Andrej.Zavratnik@sb-mb.si
authors.forename: Andrej
authors.initials: A
authors.lastname: Zavratnik
authors.forename: Janez
authors.initials: J
authors.lastname: Prezelj
authors.forename: Andreja
authors.initials: A
authors.lastname: Kocijancic
authors.forename: Janja
authors.initials: J
authors.lastname: Marc
mesh_terms: D000368:Aged; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D047628:Estrogen Receptor alpha; D008055:Lipids; D020845:Selective Estrogen Receptor Modulators; D014280:Triglycerides; D020849:Raloxifene Hydrochloride; D002784:Cholesterol