脂蛋白脂酶基因多态性与冠心病关系的研究

摘要

目的探讨脂蛋白脂酶基因的多态性与冠心病的相关性. 方法提取冠心病群体和正常群体的基因组DNA,借助聚合酶链反应扩增LPL基因的9个外显子及其侧翼的内含子序列,采用变性高效液相色谱技术对扩增的片段进行了筛查,并用双脱氧末端终止法对扩增的片段进行了DNA序列检测.结果在LPL 基因第5外显子发现了一未见文献报道的多态位点,即 G830→A转换,该变异导致LPL 基因第192 位的Arg(CGA)被Gln(CAA)取代.经χ2检验,由此多态产生的基因型A/A和等位基因A在对照组和冠心病组之间没有显著性差异(P>0.05).对冠心病患者组进一步采用χ 2检验,发现A/A基因型和A等位基因在合并有高甘油三酯/低高密度脂蛋白胆固醇血症的患者组和血脂正常的患者组之间存在显著性差异(P<0.05). 结论首次发现了LPL 基因G830A的多态性,该多态性(Arg192Gln)可能影响LPL的酶活性,导致高甘油三酯/低高密度脂蛋白胆固醇血症.该发现可能为探讨冠心病发病的分子机理有重要价值.%Objective To investigate polymorphisms in the gene for lipoprotein lipase (LPL) in Chinese populations with coronary heart disease (CHD) and to inquire into the relations hip between these polymorphisms in LPL gene and CHD. Methods Genomic DNA was extracted from patients with CHD and normal control subjects usi ng a salting out method. The entire coding region and flanking sequences of all coding exons of the LPL gene were amplified by PCR technique and PCR products w ere detected by denaturing high-performance liquid chromatography (DHPLC) and s equenced with a dideoxy terminal termination method. Results A novel polymorphic site, G830A, that is within the fifth exon of the LPL gene w as found. The 192 codon CGA was changed into CAA and resulted in the substituti on of glutamine for arginine. Between the control and CHD groups, chi-square t est showed no significant difference in the frequencies of the A/A genotype and A allele (P>0.05). However, the frequencies of A/A genotype and A allele ( 0.653 and 0.786) in CHD patients with high plasma triglyceride/lowed plasma hi gh density lipoprotein cholesterol were higher than those (0.415 and 0.642) in CHD patients without hyperlipidemia (P<0.05). Conclusion No direct association was found between the LPL Arg192Gln substitution polymor phism and CHD, but there is a significant positive correlation between the A/A g enotype of the LPL gene and CHD associated with high triglyceride/lowed high den sity lipoprotein cholesterol. This study may provide new data for exploring the molecular mechanism of CHD.