Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response
Copyright policy )Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response
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.
- University of São Paulo Brazil
- Universidade de São Paulo Brazil
- University of São Paulo Brazil
- University of Sao Paulo
- University Hospital Canada
Male, Genotype, Hypercholesterolemia, OATP; atorvastatin; single nucleotide polymorphisms; pharmacogenetics, Organic Anion Transporters, Polymorphism, Single Nucleotide, Article, Linkage Disequilibrium, Gene Frequency, Atorvastatin, Humans, Pyrroles, Aged, OATP, Liver-Specific Organic Anion Transporter 1, Anticholesteremic Agents, Single nucleotide polymorphisms, Middle Aged, Logistic Models, Haplotypes, Heptanoic Acids, Pharmacogenetics, Multivariate Analysis, Female
Male, Genotype, Hypercholesterolemia, OATP; atorvastatin; single nucleotide polymorphisms; pharmacogenetics, Organic Anion Transporters, Polymorphism, Single Nucleotide, Article, Linkage Disequilibrium, Gene Frequency, Atorvastatin, Humans, Pyrroles, Aged, OATP, Liver-Specific Organic Anion Transporter 1, Anticholesteremic Agents, Single nucleotide polymorphisms, Middle Aged, Logistic Models, Haplotypes, Heptanoic Acids, Pharmacogenetics, Multivariate Analysis, Female
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