中国人内源性高甘油三酯血症患者胆固醇酯转运蛋白基因Taq IB和-629C/A多态性

目的研究胆固醇酯转运蛋白（cholesterol ester transfer protein，CETP）基因多态性是否与中国人内源性高甘油三酯血症（hypertriglyceridemia，HTG）有关联，为探讨本病的分子遗传基础提供依据。方法应用聚合酶链反应-限制性片段长度多态性分析法，对成都地区汉族214名正常人及135例HTG患者CETP基因Taq IB和-629C／A多态性位点进行分析。结果中国人CETP基因Taq IB多态位点B2等位基因频率为0．418，-629C／A多态位点A等位基因频率为0．479。HTG组和对照组Taq IB位点和-629C／A之间等位基因的频率差异无统计学意义（0．382 vs 0．418，P〉0．05；0．489 vs 0．479，P〉0．05）。两位点连锁关系分析提示其存在强的连锁不平衡（D＇=0．881）。对照组Taq IB位点B2B2基因型携带者其血清高密度脂蛋白水平较B1B1携带者高（P〈0．05），而低密度脂蛋白较B1B2者显著降低，按性别划分为亚组后，差异仅在对照组男性存在（P〈0．05）；对照组-629C／A位点CC基因型携带者其血清低密度脂蛋白水平较AC基因型者显著降低（P〈0．01），而载脂蛋白AⅡ则显著升高（P〈0．05）。两位点联合基因型的分析显示，对照组B2B2CC基因型携带者血清高密度脂蛋白较B1B1CC型者显著升高（P〈0．05），B2B2CC型者与B1B1CC型者比较，甘油三酯水平显著降低（P〈0．05）。结论中国成都地区汉族人CETP基因Taq IB多态性与血清高密度脂蛋白、低密度脂蛋白含量有一定关联，-629C／A多态性与血清低密度脂蛋白和载脂蛋白AⅡ有一定关联，但未见这些位点与内源性高甘油三酯血症有关。

Analysis of cholesterol ester transfer protein gene Taq IB and -629 C/A polymorphisms in patients with endogenous hypertriglyceridemia in Chinese population

OBJECTIVE: To investigate the variations of cholesterol ester transfer protein (CETP) gene and its relation to endogenous hypertriglyceridemia (HTG) in Chinese population. METHODS: One hundred and thirty-five endogenous hypertriglyceridemics and 214 healthy subjects from a population of Chinese Han nationality in Chengdu area were studied using restriction fragment length polymorphism (RFLPs) amplified by polymerase chain reaction (PCR). The polymorphic sites studied included Taq IB and -629 C/A polymorphism in CETP gene. RESULTS: The frequencies of B(2) allele at Taq IB site in normal group and HTG group were 0.418 and 0.382, respectively. The frequencies of A allele at -629 C/A site in the two groups were 0.479 and 0.489, respectively. No significant difference between normal control and HTG groups were found in both allele frequency of the two polymorphism. Linkage disequilibrium was observed between Taq IB and -629 C/A polymorphic sites (D'=0.881). In the normal control group, subjects with genotype B(2)B(2) of Taq IB site had a higher serum mean concentration of HDL-C and lower LDL-C when compared with that of genotype B(1)B(1) and B(1)B(2), respectively (both P< 0.05), while those with genotype CC of -629 C/A site had a lower LDL-C level and higher Apo A II level when compared with that of genotype AC (P< 0.01 and P< 0.05, respectively). The changes of the lipid and lipoprotein levels were only observed in normal male subjects when male and female groups were further separated. No significant changes of lipid and lipoprotein levels were observed in both polymorphism in HTG group. Combined genotype analysis of the two sites, subjects with genotype B(2)B(2)CC in normal controls had higher HDL-C levels but lower serum triglyceride (TG) when compared with B(1)B(1)CC. CONCLUSION: These results suggest that Taq IB and -629 C/A polymorphisms in CETP gene are associated with healthy control subjects to some extent in Chinese population, but not with endogenous hypertriglyleridemia in the population group.