【作者】 赵郁；

【导师】 解用虹；

【作者基本信息】 天津医科大学 ， 生物化学与分子生物学， 2005， 硕士

【摘要】 脂蛋白脂肪酶（LPL）是脂蛋白分解代谢的关键酶,其主要生理功能是水解血液中富含甘油三酯脂蛋白中的三脂酰甘油,是影响CM和VLDL代谢的关键因子。LPL基因变异常可导致异常脂蛋白血症,而异常脂蛋白血症是最常见的代谢性疾病之一,也是动脉粥样硬化的重要危险因子。LPLSer447Ter变异发现于1990年,是由于LPL基因第9外显子1595碱基处的单个碱基突变（C→G）造成相应氨基酸编码由TCA（丝氨酸）突变为TGA（终止密码子）,使合成的LPL在C末端缺少了2个氨基酸（Ser-Gly）。此后许多研究者发现携带这一变异的人群较野生型人群有较低的甘油三酯（TG）水平和较高的高密度脂蛋白胆固醇（HDLc）水平,并且非冠心病人群较冠心病人群这一变异的频率更高,故认为它是一有益突变,对患者起保护性作用,但也有许多相反的意见。多年来该变异对血脂的影响一直存在争议,可能是由于样本的选择（包括样本的质与量）、遗传因素和环境因素的联合作用等使各项研究结果存有出入。为探讨中国人群LPL基因外显子9常见突变的种类、频率以及其可能产生的影响,我们利用聚合酶链反应-单链构象多态性（PCR-SSCP）分析和DNA测序技术及PCR-RFLP技术检测出我国人群的LPL外显子9基因突变、基因型和等位基因频率,确定了中国人群Ser⁴⁴⁷→stop这一多态性位点。为尽量减少各种因素的干扰,使该多态性位点对血脂影响更多还原

【Abstract】 Lipoprotein lipase （LPL） plays an important role in lipoprotein metabolism by hydrolyzing triglyceride-rich lipoproteins such as chylomicrons and very low density lipoprotein. The major deficiency of LPL can cause hypertriglyceridemia, which is often the result of gene mutations. LPLSer447Ter found in 1990 is a consequence of a C→G transversion at nucleotide 1595 in exon 9 of LPL gene, converting the serine 447 codon （TCA） to a premature termination codon （TGA）. Many researchers discovered that Ser447Ter group was associated with lower TG levels and higher HDLc levels than the controls, and to compare with the coronary group, frequency of this mutation is higher in the non- coronary group. Ser447Ter variant has been reported to have beneficial effect on TG and HDL-c in patients with CHD or normal subjects. But there are contrary opinions, the influence of this mutation upon the blood lipids exists the controversy. To investigate distribution of gene mutations in LPL exon 9 in Chinese population and to study the possible effects of the mutation on plasma lipids, variants were screened by PCR-SSCP and DNA sequencing. Ser⁴⁴⁷→stop polymorphism was identified by PCR-RFLP . the plasma lipids in stop447 carrier group and stop447 noncarrier group were compared and analysis.The frequencies of stop447 allele is 9.4% in the 420 subjects with normal TG更多还原