García-Otín A-L, Civeira F, Aristegui R, Díaz C, Recalde D, Sol J M, Masramon X, Hernández G, Pocoví M
Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Spain.
Eur J Clin Invest. 2002 Jun;32(6):421-8. doi: 10.1046/j.1365-2362.2002.00996.x.
Combined hyperlipidemia (CHL) is one of the dyslipidemias more frequently found in clinical practice, and lipid-lowering drugs are often necessary in its management. Some genetic loci have been associated with CHL expression, and some studies have shown modulation of drugs efficiency in the treatment of dyslipidemias by genetic polymorphisms. We have investigated whether common polymorphisms and mutations in the apolipoprotein (apo) E, lipoprotein lipase (LPL), and apo CIII genes influence atorvastatin or bezafibrate responses in patients with CHL.
One hundred and sixteen subjects participating in the ATOMIX study (Atorvastatin in Mixed dyslipidemia) were randomized to treatment with either atorvastatin or bezafibrate. Apolipoprotein E genotype and common -491A/T and -219T/G polymorphisms in the apo E gene promoter region, Sst I polymorphism in the apo CIII gene (3238C/G), and D9N and N291S common mutations in the LPL gene were determined by polymerase chain reaction (PCR) and restriction enzyme digestion.
Statistical analysis showed the influence of the -491A/T polymorphism in atorvastatin and bezafibrate treatments. Subjects carrying the -491T allele showed an increased LDL-cholesterol-lowering effect with atorvastatin compared with -491T allele noncarriers (-35% vs. -27%, P = 0.037). Subjects carrying the -491T allele, when on bezafibrate treatment, showed a lower triglyceride reduction compared with -491T allele noncarriers (-23% vs. -39%, P = 0.05).
In our study, the -491A/T polymorphism in the apo E gene promoter region modulated the lipid-lowering efficiency of atorvastatin and bezafibrate in CHL patients. Such influence might explain some of the interindividual response variabilities observed for the two drugs, and could help in CHL management.
混合性高脂血症（CHL）是临床实践中较常见的血脂异常之一，治疗时常需使用降脂药物。一些基因位点与CHL的表达有关，一些研究表明基因多态性可调节血脂异常治疗中药物的疗效。我们研究了载脂蛋白（apo）E、脂蛋白脂肪酶（LPL）和apo CIII基因的常见多态性和突变是否会影响CHL患者对阿托伐他汀或苯扎贝特的反应。
116名参与ATOMIX研究（混合性血脂异常中的阿托伐他汀）的受试者被随机分为阿托伐他汀或苯扎贝特治疗组。通过聚合酶链反应（PCR）和限制性内切酶消化确定apo E基因启动子区域的载脂蛋白E基因型和常见的-491A/T和-219T/G多态性、apo CIII基因的Sst I多态性（3238C/G）以及LPL基因的D9N和N291S常见突变。
统计分析显示-491A/T多态性对阿托伐他汀和苯扎贝特治疗有影响。与非-491T等位基因携带者相比，携带-49T等位基因的受试者使用阿托伐他汀时低密度脂蛋白胆固醇降低效果增强（-35%对-27%，P = 0.037）。携带-491T等位基因的受试者在接受苯扎贝特治疗时，与非-491T等位基因携带者相比，甘油三酯降低幅度较小（-23%对-39%，P = 0.05）。
在我们的研究中，apo E基因启动子区域的-491A/T多态性调节了CHL患者中阿托伐他汀和苯扎贝特的降脂效率。这种影响可能解释了这两种药物观察到的个体间反应差异，并有助于CHL的管理。
