Effect of Genetic Polymorphisms in Detoxification Proteins on Treatment Outcome of Atorvastatin

Background: The most effective method of lowering cholesterol is the administration of statins. Cholesterol-lowing effects of statin may be affected by polymorphisms of detoxification genes. Methodology: In this study, 130 adult patients suffering from hypercholesterolemia and receiving atorvastatin therapy (40 mg daily) were enrolled. At 12-15 months subsequent to treatment of atorvastatin, Total Cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and genes of cytochrome P450 (CYP) 3A4, UDP-glucuronosyltransferase (UGT) 1A1, UGT1A3, multidrug resistance proteins 1 (MDR1) and organic anion transporter polypeptides 2 (OATP2) in the study subjects were determined. Results: There were 87 and 43 subjects whose TC concentrations were <5.1 and >= 5.1 mmol L-1, respectively 93 and 37 patients whose LDL-C concentrations were <3.3 and >= 3.3 mmol L-1, respectively. Odds Ratio (OR) of wild type in the UGT1A1 gene was 0.389 (95% confidence interval = 0.174-0.873, p = 0.02) in the subjects whose TC concentrations were compared between <5.1 and >= 5.1 mmol L-1, while ORs of other haplotypes in the UGT1A1 gene (OR = 0.976-1.464, p = 0.37-0.98) and haplotypes of CYP3A4, UGT1A3, MDR1 and OATP2 genes (OR = 0.561-3.818, p = 0.14-0.99) were not statistically significant. For LDL-C concentrations, ORs of all the haplotypes of CYP3A4, UGT1A1, UGT1A3, MDR1 and OATP2 genes were not statistically significant (OR = 0.371-2.118, p = 0.06-0.93). Conclusion: Variant UGT1A1 gene is related to cholesterol-lowing effects in Taiwanese patients treated with atorvastatin. Determination of UGT1A1 gene can be considered for the selection of effective-outcome patients prior to giving of atorvastatin.