Cenarro Ana, Artieda Marta, Gonzalvo Carmen, Meriño-Ibarra Erardo, Arístegui Rosa, Gañán Alberto, Díaz Cristina, Sol Josep María, Pocoví Miguel, Civeira Fernando
Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Zaragoza, Spain.
Am Heart J. 2005 Dec;150(6):1154-62. doi: 10.1016/j.ahj.2005.02.006.
Combined hyperlipidemia (CHL) is a very frequent dyslipidemia, being lipid-lowering drugs often necessary in its management. Some genetic loci have been associated with CHL, and modulation of lipid-lowering treatment by genetic polymorphisms has been reported. We have investigated whether common polymorphisms in the hepatic lipase gene (LIPC) influence the baseline lipid concentration and the response to atorvastatin or bezafibrate in patients with CHL.
Two genetic polymorphisms in LIPC (-514C-->T and +651A-->G) were determined by polymerase chain reaction and restriction analysis in 118 subjects of the ATOMIX (Atorvastatin in Mixed dyslipidemia) study who were randomized to treatment with either atorvastatin or bezafibrate and in 114 normolipidemic controls.
The -514T allele frequency was higher in the ATOMIX group (0.297) than in the control group (0.193) (P = .01). The -514T allele carriers in the control group showed higher high-density lipoprotein cholesterol (HDL-C) concentrations than the -514C homozygotes, 50.8 +/- 1.86 versus 45.9 +/- 1.40 mg/dL (P = .02). The +651G carriers in the ATOMIX group showed lower total cholesterol and low-density lipoprotein cholesterol than the +651A homozygotes, 274 +/- 3.72 and 181 +/- 3.50 mg/dL versus 289 +/- 4.0 and 194 +/- 3.76 mg/dL, respectively (P < .01). Homozygotes for the -514C allele on bezafibrate treatment had greater decrease in triglycerides and greater increase in HDL-C than -514T allele carriers after 12 months of bezafibrate treatment, -39.4% and +35.8% versus -25.5% and +20.4%, respectively (P = .080 and P = .007, respectively).
A higher frequency of the -514T allele of LIPC suggests a role of this locus in the pathogenesis of CHL. The -514T allele is associated with higher HDL-C concentration in normolipidemic population. The -514C-->T polymorphism modulates the lipid-lowering response to bezafibrate, with a better effect in homozygous CC subjects.
混合性高脂血症（CHL）是一种非常常见的血脂异常，在其治疗中通常需要使用降脂药物。一些基因位点已与CHL相关联，并且已有报道基因多态性对降脂治疗的调节作用。我们研究了肝脂酶基因（LIPC）中的常见多态性是否会影响CHL患者的基线血脂浓度以及对阿托伐他汀或苯扎贝特的反应。
通过聚合酶链反应和限制性分析，在ATOMIX（混合性血脂异常中的阿托伐他汀）研究的118名受试者中确定了LIPC基因的两种基因多态性（-514C→T和+651A→G），这些受试者被随机分配接受阿托伐他汀或苯扎贝特治疗，同时选取了114名血脂正常的对照者。
ATOMIX组中-514T等位基因频率（0.297）高于对照组（0.193）（P = 0.01）。对照组中-514T等位基因携带者的高密度脂蛋白胆固醇（HDL-C）浓度高于-514C纯合子，分别为50.8±1.86与45.9±1.40mg/dL（P = 0.02）。ATOMIX组中+651G携带者的总胆固醇和低密度脂蛋白胆固醇低于+651A纯合子，分别为274±3.72和181±3.50mg/dL与289±4.0和194±3.76mg/dL（P < 0.01）。在接受苯扎贝特治疗12个月后，-514C等位基因纯合子患者的甘油三酯下降幅度更大，HDL-C升高幅度也大于-514T等位基因携带者，分别为-39.4%和+35.8%与-25.5%和+20.4%（P分别为0.080和0.007）。
LIPC基因-514T等位基因的较高频率表明该位点在CHL发病机制中起作用。-514T等位基因与血脂正常人群中较高的HDL-C浓度相关。-514C→T多态性调节对苯扎贝特的降脂反应，在CC纯合子受试者中效果更好。
