Fiegenbaum Marilu, da Silveira Fabiano R, Van der Sand Cézar R, Van der Sand Luiz Carlos, Ferreira Maria E W, Pires Renan C, Hutz Mara H
Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Clin Chim Acta. 2005 Dec;362(1-2):182-8. doi: 10.1016/j.cccn.2005.06.005. Epub 2005 Jul 20.
In recent years, one of the focuses of genetic investigation in cardiology has been to identify the genetic factors associated with variable response to statin treatment. Polymorphisms in apolipoprotein E (APOE), cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC), proteins with major roles in lipid metabolism and homeostasis have been shown associated with lipid-lowering drugs response.
One hundred forty-six hypercholesterolemic patients of European descent were prospectively enrolled and treated with simvastatin 20 mg per day for over 6 months. Ninety-nine subjects completed the 6-month follow-up. Plasma lipids and lipoproteins were measured before and throughout the study. APOE (E2, E3 and E*4), LIPC-250A > G and CETP TaqIB genotypes were determined by PCR and restriction mapping.
After a 6-month follow-up, no differences among genotypes in the percentage variation in lipid and lipoprotein concentrations for APOE and LIPC SNPs were observed. After adjustment for covariates, CETP B2B2 homozygotes showed a greater HDL-cholesterol increase compared to B1B2 and B1B1 subjects (14.1% vs. 1.7% and 1.3%, P < 0.05, respectively).
Our study demonstrates that individual plasma HDL-cholesterol response to simvastatin is mediated, in part, by the CETP gene locus, with the B2 homozygotes having more benefit in HDL-C improvement than carriers of B1 allele.
近年来，心脏病学基因研究的重点之一是确定与他汀类药物治疗反应差异相关的遗传因素。载脂蛋白E（APOE）、胆固醇酯转运蛋白（CETP）和肝脂酶（LIPC）的多态性，这些在脂质代谢和体内平衡中起主要作用的蛋白质已被证明与降脂药物反应有关。
前瞻性招募了146名欧洲血统的高胆固醇血症患者，每天服用20mg辛伐他汀治疗超过6个月。99名受试者完成了6个月的随访。在研究前及整个研究过程中测量血脂和脂蛋白。通过聚合酶链反应（PCR）和限制性图谱分析确定APOE（E2、E3和E*4）、LIPC-250A>G和CETP TaqIB基因型。
经过6个月的随访，未观察到APOE和LIPC单核苷酸多态性（SNP）基因型在脂质和脂蛋白浓度变化百分比上的差异。在对协变量进行调整后，与B1B2和B1B1受试者相比，CETP B2B2纯合子的高密度脂蛋白胆固醇（HDL-C）升高幅度更大（分别为14.1%对1.7%和1.3%，P<0.05）。
我们的研究表明，个体血浆HDL-C对辛伐他汀的反应部分由CETP基因位点介导，B2纯合子在改善HDL-C方面比B1等位基因携带者更有益。
