中国人内源性高甘油三酯血症患者载脂蛋白AⅣ基因变异的研究

Variations of apolipoprotein A Ⅳ gene in Chinese endogenous hypertriglyceridemics

目的 探讨载脂蛋白 A (apolipoprotein A ,apo A )基因变异是否与中国人内源性高甘油三酯血症有关联 ,为其分子遗传基础提供依据。方法 应用多聚酶链反应 -限制性片段长度多态性及DNA片段序列分析法 ,对成都地区汉族 171名正常人及 10 6例内源性高甘油三酯血症 (hypertri glyc-eridemia,HTG)患者 apo A 基因多态性进行了研究。检测的 apo A 基因位点有 :密码子 9(A→ G突变 ,同义突变 ) ,密码子 34 7(A→T突变 ,错义突变 )、密码子 36 0 (G→T突变 ,错义突变 )及 Msp (内含子 2 C→T突变 )。结果 与正常对照组比较 ,HTG组密码子 9的 G等位基因频率显著升高 (0 .45 3vs0 .36 6 ,P<0 .0 5 ) ,其它位点等位基因频率未见差异 (P>0 .0 5 )。中国人 apo A 基因密码子 9、密码子 34 7和密码子 36 0等位点相应的 G等位基因、T等位基因和 T等位基因频率与欧洲白种人存在明显种族差异 (0 .36 6 vs 0 .0 32 ,P<0 .0 0 1;0 .0 0 0 vs0 .16 0 ,P<0 .0 0 1;0 .0 0 0 vs0 .0 70 ,P<0 .0 0 1)。与日本人比较 ,上述位点的等位基因频率及 Msp 位点 T等位基因频率均差异无显著性 (P>0 .0 5 )。正常男性 apo A 基因密码子 9位点G/G基因型携带者其血清 apo A 水平显著高于 A/A基因型携带者 (P<0 .0 1) ;而 HTG组 Msp

Objective The aim of this study was to investigate variations of apolipoprotein AⅣ(apo AⅣ) gene and its relation to endogenous hypertriglyceridemia(HTG) in Chinese population. Methods One hundred and six endogenous hypertriglyceridemics and 171 healthy subjects from a population of Chinese Han nationality in Chengdu area were studied using restriction fragment length polymorphisms (RFLPs) and sequencing of apoAⅣ gene amplified by polymerase chain reaction (PCR). The polymorphic sites of apoAⅣ gene studied included codon 9 (A→G, synonymous mutation), codon 347 (A→T, non-synonymous mutation), codon 360 (G→T, non-synonymous mutation), and Msp Ⅰ polymorphism (CC/TGG) within intron 2. Results The frequency of G allele at codon 9 in HTG group was higher than that in healthy controls(0.453 vs 0.366, P <0.05). The other polymorphic sites showed no significant differences of the allele frequencies between the two groups. The frequencies of rare alleles, such as G allele at codon 9, T allele at codon 347 and T allele at codon 360 polymorphic site were significantly different from those reported in European Caucasians (0.366 vs 0.032, P <0.001, 0.000 vs 0.160, P <0.001; 0.000 vs 0.070, P <0.001), but no differences were found when compared with those in Japanese, including Msp Ⅰ site ( P >0.05). In the healthy male control group, subjects with genotype G/G of codon 9 had a higher serum mean concentration of apoAⅠ when compared with that of genotype A/A ( P <0.01). In the HTG group, subjects with genotype C/T of Msp Ⅰ site had a higher serum mean concentration of TG with compared with those with genotype C/C and T/T ( P <0.05). This difference was only observed in male HTG group when male and female subgroups were further separated. Conclusion These results suggest that Msp Ⅰ and codon 9 polymorphism in apoAⅣ gene are associated with endogenous hypertriglyceridemia to some extent in Chinese population.