正常中国人及内源性高甘油三酯血症患者内皮脂酶基因启动子-384A〉C多态性的研究

The - 384A 〉 C polymorphism of endothelial lipase gene promoter region in Chinese healthy normolipidemic and endogenous hypertriglyceridemic subjects

目的研究内皮脂酶基因启动子-384A〉C位点多态性与正常汉族中国人及内源性高甘油三酯血症（hypertriglyceridemia，卜兀℃）患者血脂及载脂蛋白水平是否存在关联，为探讨HTG发病的分子遗传基础提供依据。方法采用聚合酶链反应-限制性片段长度多态性分析法对214名正常人和103例HTG患者内皮脂酶基因-384A〉C位点多态性进行分析，采用酶法和单向免疫扩散法对血脂和载脂蛋白水平进行测定。结果中国人内皮脂酶基因-384A〉C多态位点C等位基因频率为0．178，与日本人的0．119和日裔美国人的0．115比较，差异有统计学意义（P〈0．01，P〈0．01）。未见正常人和HTG患者之间C等位基因频率存在差异（P〉0．05）。正常中国人C等位基因携带者（AC及CC型者）血清总胆固醇、低密度脂蛋白胆固醇及非高密度脂蛋白胆固醇水平均较AA基因型者显著升高（5．234-0．74mmol／L vs 4．93±0．74mmol／L，P=0．025；3．27±0．74mmol／L vs 2．98±0．80mmol／L，P=0．038；3．81±0．73mmol／LVS3．49±0．85mmol／L，P=0．031）；进一步按性别划分为男女亚组后，这种差异仅在女性亚组存在。未见该多态性与高密度脂蛋白胆固醇及其它血脂和载脂蛋白水平存在关联。对HTG患者的研究未发现-384A〉C多态性与血脂及载脂蛋白水平有关。结论内皮脂酶基因-384A〉C多态性与成都地区正常汉族中国人血清总胆固醇、低密度脂蛋白-胆固醇及非高密度脂蛋白-胆固醇水平有关联，但未见其与HTG患者血脂及载脂蛋白水平有关。

Objective To investigate the effects of the - 384A 〉 C polymorphism in the promoter region of endothelial lipase （EL） gene on serum lipid and apolipoprotein levels in healthy normolipidemic（HTG） and endogenous hypertiglyceridemic （HTG） subjects. Methods Two hundred and fourteen healthy normolipidemic and 103 endogenous hypemiglycefidemic subjects from a population of Chinese Han nationality in Chengdu area were studied using restriction fragment length polymorphism （RFLPs）. Serum lipids were measured by enzymatic kits and apolipoproteins A Ⅰ, A Ⅱ , B100, C Ⅱ, C Ⅲ and E were measured by the radial immunadiffussion kits. Results The frequency of the C allele at the - 384A〉 C site in EL gene in the population （0. 178） was higher than that of Japanese population （0. 119） and Japanese Americans （0.115 ） （ P 〈 0.01 and P 〈 0.01 ）, respectively. No significant difference between normolipidemic and HTG groups was found in both allele and genotype frequencies. In normal group, subjects of the C allele carriers （A/C and C/C genotype carriers） had a higher serum mean concentration of TC, LDL-C and nHDL-C when compared with those of genotype AA （ 5.23 ± 0.74 mmol/L vs 4.93 ± 0.74 mmol/L, P = 0. 025 ; 3.27 ±0.74 mmol/L vs 2.98± 0.80 mmol/L, P = 0. 038 ; 3.81 ± 0.73 mmol/L vs 3.49± 0.85 mmol/L, P = 0.031, respectively）. Similar result was only observed in female subgroup when male and female subgroups were further separated. No significant changes of lipid and lipoprotein levels were observed in the polymorphism in HTG group. Conclusion These results suggest that the - 384A 〉 C polymorphism in the promoter region of the endothelial lipase gene is associated with serum TC, LDL-C, and nHDL-C levels in healthy Chinese subjects in Chengdu area, but not associated with the lipid levels in the endogenous hypertriglyceridmic group.