胆固醇酯转运蛋白基因突变及其与冠状动脉粥样硬化性心脏病易感性的关联研究

目的：确定胆固醇酯转运蛋白（cholesteryl ester transfer protein,CETP)基因4种突变在中国人群中的频率，并探讨这些突变与脂代谢和冠状动脉粥样硬化性心脏病（coronary atherosclerotic heart disease,CHD)易感性的关系。方法：对209名正常人和203例CHD患者CETP基因相应片段进行了限制性片段长度多态性分析，用HWE软件和SPSS软件分别进行遗传平衡检验和统计学分析。结果：在正常对照组和CHD患者组中均未检出IVS14A和451Q突变基因。405V突变基因频率在正常人和CHD患者中分别为0．443和0．413，442G突变基因频率在两组中分别为0．007和0．025，I405V和D442G突变的等位基因频率分布符合Hardy-Weinberg平衡。CHD患者组442G突变基因频率显著高于正常人群（P＝0．043）。与无D442G突变的CHD患者相比，442G突变杂合子CHD患者的总胆固醇和低密度脂蛋白胆固醇显著升高（P＝0．017；P＝0．041）。结论：CETP基因IVS14A和451Q突变在中国人群中非常罕见，442G突变基因可能是中国人CHD的易感因子之一。

Study on the association of cholesteryl ester transfer protein gene mutations with the susceptibility to coronary atherosclerotic heart disease

Objective To determine the frequencies of 4 mutations of cholesteryl ester transfer protein (CETP) gene in Chinese population and to investigate the association of the mutations with lipid metabolism and the susceptibility to coronary atherosclerotic heart disease (CHD). Methods The target fragments of CETP gene were amplified and analyzed by PCR restriction fragment length polymorphism technique in 209 unrelated control individuals and 203 CHD patients. The test for Hardy Weinberg equilibrium was performed using HWE program and statistical analysis was implemented in statistical package SPSS. Results IVS14A and 451Q mutant genes were not found in either control group or patient group. The frequencies of 405V mutant allele were 0.443 and 0.413 in controls and patients, respectively, while 442G mutant gene frequencies were 0.007 and 0.025, respectively. The observed allele frequencies of I405V and D442G mutation were in accord with Hardy Weinberg equilibrium. The frequency of 442G mutant gene in patients was significantly higher than that in controls ( P =0.043). Compared with the CHD patients without D442G mutation, the 442G heterozygous CHD patients exhibited a significant increase in plasma TC and LDL C concentration ( P =0.017; P =0.041). Conclusion IVS14A and 451Q mutants of CETP gene were rare in Chinese population and 442G mutant gene was possibly one of the susceptibility factors to CHD in Chinese.