Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response.

Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil; E-Mails: (P.M.S.P.); (V.N.S.); (F.D.V.G.); (M.A.V.W.); (S.S.A.); (A.D.L.); (M.H.H.); (R.D.C.H.).
International Journal of Molecular Sciences (Impact Factor: 2.46). 01/2011; 12(9):5815-27. DOI: 10.3390/ijms12095815
Source: PubMed

ABSTRACT The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated.
One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot(®) and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (-71T>C) gene polymorphisms were identified by TaqMan(®) Real-time PCR.
Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3-8.0, p < 0.05).
SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy.

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