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Int J Mol Sci. 2011;12(9):5815-27. doi: 10.3390/ijms12095815. Epub 2011 Sep 9.

Pharmacogenetics of OATP transporters reveals that SLCO1B1 c.388A>G variant is determinant of increased atorvastatin response.

Author information

1
Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil; E-Mails: paulamsp@gmail.com (P.M.S.P.); viviansilbiger@hotmail.com (V.N.S.); fdallavecchia@yahoo.com.br (F.D.V.G.); malicewi@usp.br (M.A.V.W.); sisorkin@usp.br (S.S.A.); adluchessi@uol.com.br (A.D.L.); mhhirata@usp.br (M.H.H.); rosariohirata@usp.br (R.D.C.H.).

Abstract

AIMS:

The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated.

MATERIAL AND METHODS:

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.

RESULTS:

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).

CONCLUSION:

SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy.

KEYWORDS:

OATP; atorvastatin; pharmacogenetics; single nucleotide polymorphisms

PMID:
22016628
PMCID:
PMC3189752
DOI:
10.3390/ijms12095815
[Indexed for MEDLINE]
Free PMC Article
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