Determinants of variable response to simvastatin treatment:: the role of common variants of SCAP, SREBF-1a and SREBF-2 genes
Determinants of variable response to simvastatin treatment:: the role of common variants of SCAP, SREBF-1a and SREBF-2 genes
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DOI：
10.1038/sj.tpj.6500334
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发表时间：
2005-01-01
影响因子：
2.8
通讯作者：
Hutz, MH
中科院分区：
文献类型：
--
作者：
Fiegenbaum, M;Silveira, FR;Hutz, MH
我们研究了固醇调节元件结合因子-1a和-2（SREBF-1a和SREBF-2）和SREBF裂解激活蛋白（SCAP）基因单核苷酸多态性对辛伐他汀降脂反应的影响。总共有146例欧洲血统的高胆固醇血症患者接受辛伐他汀20 mg/天的前瞻性治疗超过6个月。其中99例受试者完成了6个月随访。在研究前和整个研究期间测量血浆脂质和脂蛋白。SCAP 2386 G等位基因携带者血浆总胆固醇（TC）的平均下降百分比大于2386 A等位基因纯合子携带者（-29.6 +/- 13.4 vs - 22.1 +/-13.8%，P = 0.007）。大约61%的2386 G携带者对TC水平的反应高于平均水平（Δ TC - 27.8%），而2386 A纯合子只有29%达到这种降低（P = 0.009）。我们的数据表明，SCAP 2386 A4 G基因多态性是辛伐他汀治疗的TC和甘油三酯反应的重要预测因子。
We investigated the effect of single-nucleotide polymorphisms in sterol regulatory element-binding factors-1a and - 2 (SREBF-1a and SREBF-2) and SREBF cleavage-activating protein ( SCAP) genes on lipid-lowering response to simvastatin. In all, 146 hypercholesterolemic patients of European descent were prospectively treated with simvastatin 20 mg/day for over 6 months. Of these 99 subjects completed the 6-month follow-up. Plasma lipids and lipoproteins were measured before and throughout the study. The mean percentage decrease in plasma total cholesterol (TC) was greater in subject carriers of SCAP 2386G allele compared with those homozygous for 2386A allele (- 29.6 +/- 13.4 vs - 22.1 +/- 13.8%, P = 0.007). About 61% of the 2386G carriers were above-average responders for TC levels (Delta TC - 27.8%), whereas only 29% of 2386A homozygous reached this reduction ( P = 0.009). Our data suggest that the SCAP 2386A4G gene polymorphism was a significant predictor of TC and triglyceride responses to simvastatin treatment.