Lipid-lowering response of the HMG-CoA reductase inhibitor fluvastatin is influenced by polymorphisms in the low-density lipoprotein receptor gene in Brazilian patients with primary hypercholesterolemia.
Although the efficacy of fluvastatin (HMG-CoA reductase inhibitor) in the treatment of primary hypercholesterolemia is well documented, a wide interindividual variation treatment response has been observed. We have studied the possible role of the AvaII (exon 13), HincII (exon 12), and PvuII (intron 15) polymorphisms at the low-density lipoprotein receptor (LDLR) gene on lipid-lowering response in 55 patients (36 to 70 years old) with primary hypercholesterolemia treated with fluvastatin for 16 weeks. LDLR genotypes were determined by PCR-RFLP. The results indicate that the AvaII and PvuII polymorphisms influence the cholesterol-lowering response of the HMG-CoA reductase inhibitor Fluvastatin. Patients carrying A+A+ (AvaII) or P1P1 (PvuII) homozygous genotypes presented lower reduction in total cholesterol, LDL-C and apolipoprotein B levels after 16 weeks of treatment with fluvastatin, when compared to other genotypes (P<0.05). Our data also support the previous assumption that the AvaII, HincII, and PvuII polymorphisms of the LDLR gene are associated with variation of serum cholesterol levels. Therefore, the identification of the LDLR genetic profile may provide better prediction of a patient's clinical response to fluvastatin.
Salazar
L A
LA
Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. luisn@usp.br
Hirata
M H
MH
Quintão
E C
EC
Hirata
R D
RD
D001938:Brazil; D008076:Cholesterol, HDL / Q000097:blood; D015252:Deoxyribonucleases, Type II Site-Specific; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage*; D005260:Female; D000077340:Fluvastatin; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011973:Receptors, LDL / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011973:Receptors, LDL; D014280:Triglycerides; D000077340:Fluvastatin; C025630:CAGCTG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; C024400:GTYRAC-specific type II deoxyribonucleases