title: The farnesoid X receptor -1G>T polymorphism influences the lipid response to rosuvastatin.
abstract: The bile acid-activated nuclear receptor farnesoid X receptor (FXR) plays an important role in lipid and glucose metabolism, and in addition, it regulates multiple drug transporters involved in statin disposition. We examined whether a functional single nucleotide polymorphism (SNP) in FXR (-1G>T) influenced the lipid-lowering effect of rosuvastatin. In 385 Chinese patients with hyperlipidemia who had been treated with rosuvastatin 10 mg daily for at least 4 weeks, the association between the FXR -1G>T SNP and lipid response to rosuvastatin was analyzed. The FXR -1G>T SNP was not associated with baseline lipids but was significantly associated with the LDL cholesterol (LDL-C) and total cholesterol response to rosuvastatin. Carriers of the T-variant allele (GT+TT = 68+3) had 4.4% (95% CI: 1.2, 7.5%, P = 0.006) and 2.6% (95% CI: 0.3, 5.0%; P < 0.05) greater reductions in LDL-C and total cholesterol, respectively, compared with those with homozygous wild-type alleles. The association between the FXR polymorphism and the LDL-C response to rosuvastatin remained significant after adjusting for other covariants. This association of the variant allele of the FXR -1G>T polymorphism with a greater LDL-C response to rosuvastatin may suggest that this polymorphism influences the expression of the hepatic efflux transporters involved in biliary excretion of rosuvastatin.
authors.affiliation: Department of Medicine and Therapeutics,  Chinese University of Hong Kong, Prince of Wales Hospital, Shatin,  Hong Kong SAR.
authors.forename: Miao
authors.initials: M
authors.lastname: Hu
authors.forename: Sandra S H
authors.initials: SS
authors.lastname: Lui
authors.forename: Lai-Shan
authors.initials: LS
authors.lastname: Tam
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Li
authors.forename: Brian
authors.initials: B
authors.lastname: Tomlinson
mesh_terms: D000483:Alleles; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D002784:Cholesterol; D005464:Fluorobenzenes; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides; D000099150:Receptor, Farnesoid X-Activated