脂蛋白脂肪酶外显子9基因突变研究

Study on Gene Mutations of Exon9in Lipoprotein Lipase Gene

目的 :筛查国人脂蛋白脂肪酶 (LPL)外显子9基因突变和Ser447→stop突变频率 ,并探讨该突变对血脂水平的影响。方法 :依血脂测定结果 ,将169例分为高甘油三酯血症组(HTG组 ) ,48例和正常甘油三酯组(对照组 )121例 ,利用聚合酶链反应 -单链构象多态性和聚合酶链反应 -限制性片段长度多态性分析技术对待测人群的LPL基因外显子9及其相邻内含子区域进行突变筛查 ,并对典型单链构象电泳图谱携带者进行PCR产物测序。结果 :在169例中检出1例Ser447→stop突变纯合子 ,50例Ser447→stop杂合子 ,未检出其它位点的突变 ;HTG组的Ser447→stop突变检出率 (25.0 % ,12/48)明显低于对照组 (31.4 % ,38/121) ,HTG组的Stop447 等位基因频率(12.5% )明显低于对照组 (16.5% ),两组比较差别均有统计学意义(P<0.01)。结论 :我国人群中LPL外显子9突变种类单一 ,Ser447→stop是一高频率的多态性位点 ,Stop447等位基因可能有轻微的降低血浆甘油三酯的作用。

Objective:To study the gene mutations of exon9in lipoprotein lipase(LPL)gene.Methods:According to the finding of blood-lipid,169persons were divided into a hypertriglyceridemia(HTG)group(n=48)and a control group(n=121).The exon9in LPL gene(exon9,intron=exon boundaries)was examined by PCR-SSCP analysis,and the PCR products showing abnormal pattern on SSCP were sequenced using dideoxy-mediated chain-termination method.Results:In HTG group,12heterozygous mutations were found.In control group,1homozygous and38heterozygous mutations were found.The frequency of Ser 447 →stop in HTG group was lower than that in control group(P<0.01).Conclusion:The Ser 447 →stop is only one mutational hot site in LPL exon9,and the Ser 447 →stop polymorphism may have the tiny role to decrease plasma triglycerides.