有机阴离子转运多肽（OATP）转运体的药物遗传学研究表明，SLCO1B1基因c.388A>G变异是阿托伐他汀反应增强的决定因素。
Pharmacogenetics of OATP transporters reveals that SLCO1B1 c.388A>G variant is determinant of increased atorvastatin response.
作者信息
Rodrigues Alice C, Perin Paula M S, Purim Sheila G, Silbiger Vivian N, Genvigir Fabiana D V, Willrich Maria Alice V, Arazi Simone S, Luchessi Andre D, Hirata Mario H, Bernik Marcia M S, Dorea Egidio L, Santos Carla, Faludi Andre A, Bertolami Marcelo C, Salas Antonio, Freire Ana, Lareu Maria V, Phillips Christopher, Porras-Hurtado Liliana, Fondevila Manuel, Carracedo Angel, Hirata Rosario D C
机构信息
Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil; E-Mails:
出版信息
Int J Mol Sci. 2011;12(9):5815-27. doi: 10.3390/ijms12095815. Epub 2011 Sep 9.
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.
目的
研究溶质载体有机阴离子转运体1B1（SLCO1B1）和溶质载体有机阴离子转运体2B1（SLCO2B1）基因变异与阿托伐他汀降脂反应之间的关系。
材料与方法
选取136例无亲缘关系的高胆固醇血症患者，给予阿托伐他汀（10mg/天，共4周）治疗。通过SNaPshot（®）技术使用一组祖先信息标记对其进行基因分型，以估计个体非洲祖先成分（ACA），并通过TaqMan（®）实时荧光定量PCR鉴定SLCO1B1（c.388A>G、c.463C>A和c.521T>C）及SLCO2B1（-71T>C）基因多态性。
结果
携带SLCO1B1 c.388GG基因型的受试者相对于携带c.388AA+c.388AG基因型的受试者，其低密度脂蛋白（LDL）胆固醇降低幅度显著更高（41%对37%，p = 0.034）。单倍型分析显示，SLCO1B1*15（c.521C和c.388G）变异的纯合子相对于杂合子和非携带者对他汀类药物的反应相似。多因素logistic回归分析证实，在研究人群中，c.388GG基因型与更高的LDL胆固醇降低相关（比值比：3.2，95%置信区间：1.3 - 8.0，p < 0.05）。
结论
SLCO1B1 c.388A>G多态性导致阿托伐他汀反应显著增加，可能是预测降脂治疗疗效的重要标志物。
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