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

被引：58
作者：
Rodrigues, Alice C. [1 ]
Perin, Paula M. S. [1 ]
Purim, Sheila G. [2 ]
Silbiger, Vivian N. [1 ]
Genvigir, Fabiana D. V. [1 ]
Willrich, Maria Alice V. [1 ]
Arazi, Simone S. [1 ]
Luchessi, Andre D. [1 ]
Hirata, Mario H. [1 ]
Bernik, Marcia M. S. [3 ]
Dorea, Egidio L. [3 ]
Santos, Carla [4 ,5 ]
Faludi, Andre A. [6 ]
Bertolami, Marcelo C. [6 ]
Salas, Antonio [5 ]
Freire, Ana [5 ]
Lareu, Maria V. [5 ]
Phillips, Christopher [5 ]
Porras-Hurtado, Liliana [5 ]
Fondevila, Manuel [5 ]
Carracedo, Angel [5 ]
Hirata, Rosario D. C. [1 ]
机构：
[1] Univ Sao Paulo, Fac Pharmaceut Sci, BR-05508900 Sao Paulo, Brazil
[2] Life Technol, BR-04311000 Sao Paulo, Brazil
[3] Univ Sao Paulo, Univ Hosp, BR-05508000 Sao Paulo, Brazil
[4] Univ Aveiro, Dept Biol, P-3810193 Aveiro, Portugal
[5] Univ Santiago de Compostela, Inst Legal Med, Forens Genet Unit, Galicia 15705, Spain
[6] Dante Pazzanese Inst, BR-04012909 Sao Paulo, Brazil
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2011年 / 12卷 / 09期
基金：
巴西圣保罗研究基金会;
关键词：
OATP; atorvastatin; single nucleotide polymorphisms; pharmacogenetics; SINGLE NUCLEOTIDE POLYMORPHISMS; LIPID-LOWERING EFFICACY; ENCODING OATP1B1; C SLC21A6; PHARMACOKINETICS; PRAVASTATIN; ABCB1; PITAVASTATIN; CHOLESTEROL; HAPLOTYPES;
D O I：
10.3390/ijms12095815
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 (R) and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (-71T>C) gene polymorphisms were identified by TaqMan (R) 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.
引用
收藏
页码：5815 / 5827
页数：13
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