ATP binding cassette transporter G5 and G8 genotypes and plasma lipoprotein levels before and after treatment with atorvastatin
ATP binding cassette transporter G5 and G8 genotypes and plasma lipoprotein levels before and after treatment with atorvastatin
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DOI：
10.1194/jlr.m300278-jlr200
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发表时间：
2004-04-01
影响因子：
6.5
通讯作者：
Schaefer, EJ
中科院分区：
文献类型：
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作者：
Kajinami, K;Brousseau, ME;Schaefer, EJ
他汀类药物治疗反应的个体间差异的机制仍不确定。已有研究表明，肝脏胆固醇合成与ATP结合盒转运体G5和G8（ABCG5/8）的活性有关。为了验证ABCG5/8的基因变异可能影响他汀类药物治疗的血浆脂质反应这一假设，我们在338名接受10mg阿托伐他汀治疗的高胆固醇血症患者中检测了ABCG5/8基因座的5个非同义多态性（Q604E、D19H、Y54C、T400K和A632V）。在D19H变异的携带者中，治疗后低密度脂蛋白胆固醇（LDL - C）的值和调整后的百分比降低的平均值分别显著低于（P = 0.028）和高于（P = 0.036）非携带者（分别为112mg/dl，39.7%和119mg/dl，36.2%），而总胆固醇百分比降低方面未观察到显著差异。逐步多元回归分析显示，D19H基因型与治疗后LDL - C水平的绝对值或百分比降低之间存在显著且独立的关联。其他多态性与治疗效果无显著关联。这些结果表明，在高胆固醇血症患者中，ABCG8 D19H变异与阿托伐他汀治疗降低LDL - C的反应更强有关。
The mechanisms responsible for interindividual variation in response to statin therapy remain uncertain. It has been shown that hepatic cholesterol synthesis is associated with ATP binding cassette transporter G5 and G8 (ABCG5/8) activities. To test the hypothesis that genetic variation in ABCG5/8 might influence the plasma lipid response to statin therapy, we examined five nonsynonymous polymorphisms at the ABCG5/8 loci (Q604E, D19H, Y54C, T400K, and A632V) in 338 hypercholesterolemic patients treated with 10 mg atorvastatin. In carriers of the D19H variant, means of posttreatment values and adjusted percent reductions in LDL cholesterol (LDLC) were significantly lower (P = 0.028) and greater (P = 0.036) (112 mg/dl, 39.7%) than those of noncarriers (119 mg/dl, 36.2%), respectively, while no significant difference was observed in percent reductions in total cholesterol. Stepwise multiple regression analysis revealed significant and independent associations with absolute or percent reduction between D19H genotype and posttreatment LDL cholesterol levels. The other polymorphisms were not significantly associated with treatment effects. These results suggest that, in patients with hypercholesterolemia, the ABCG8 D19H variant is associated with greater LDLC-lowering response to atorvastatin therapy.