载脂蛋白AI—CⅢ基因区域DNA多态性及单倍型与冠心病的关系  

DNA Polymorphisms and Haplotypes in the apoAI-CIII Gene Region and Coronary Heart Disease

作　　者：孟祥文[1] 张贵寅[1] 李璞[1] 杜杨柱 

机构地区：[1]哈尔滨医科大学医学遗传学研究室

出　　处：《Acta Genetica Sinica》1990年第6期411-417,共7页

基　　金：国家自然科学基金

摘　　要：本文利用重组DNA技术,以人apoAI cDNA片段为探针,对50例正常血脂汉族个体和33例冠心病患者的载脂蛋白AⅠ—CⅢ基因区域DNA多态频率和特征进行了分析。发现中国汉族群体载脂蛋白AⅠ—CⅢ基因区域亦存在Sst-Ⅰ和Msp-Ⅰ多态位点,可产生S_2和M_22种多态片段,其等位基因频率分别为0.167和0.22,均高于高加索人但低于日本人,表明这2个多态部位的等位基因频率具有种族差异。我们还对44例正常血脂个体和27例冠心病患者进行了单倍型分析,没有发现S_1S_2M_1M_1,S_2S_2M_1M_2和S_2S_2M_1M_1基因型个体,因此,在中国汉族人群中,可能仅存在3种单倍型:S_1—M_1(0.81),S_2M_2(0.17)及S_1—M_2(0.02),而不存在S_2—M_1这种单倍型。同日本人和高加索一样,在中国汉族人群中,S_1S_2与M_1、M_2之间亦存在连锁不平衡。本研究结果表明,S_2与M_2等位基因在正常血脂的汉族人与冠心病病人之间的分布频率均没有显著差异,但冠心痛病人的S_1—M_2单倍型频率明显高于正常人,其有极显著的差异。提示S_1—M_2这种单倍型与冠心病有明显的关联,可做为一种假定的动脉粥样硬化致病基因的连锁标记,对有关个体进行连锁分析。Polymorphisms and haplotypes identified by DNA Restriction Fragment Length Polymorphisms in the apoAl-CⅢ gene region were investigated both in 33 Chinese patients with coronary heart disease and 50 unrelated healthy subjects, using genomic DNA hybridization analysis with a 1.0 kb fragment of the human apoAl gene cDNA. The frequencies of the S2 and MI alleles were 0.167 and 0.22 in healthy subjects, 0.11 and 0.24 in patients respectively. There were no differences in the frequencies of the S2 and M2 alleles between patients and healthy subjects. Since none of the subjects had the genotypes, S1S2M1M1, S2S2M1M2 and S1S2MlM1, all of the S2 alleles were considered to be associated with the M, alleles at least in Chinese population. The alleles identified by the apoClll Sst-l and apoAl Msp-l polymorphisms are in linkage disequilibrium. The individuals with the haplotype Si-A/i were significantly increased in patients compared with the ones in healthy subjects (26% versus 4.6%; X2 = 6.91, d.f = 1, P<0.01). The results of the present study suggest that both the apoCⅢ Sst-I and apoAl Msp-l polymorphisms may be a ureful genetic marker for the analysis of apoAI-CⅢ gene complex and the haplotype S1-M2 may be a useful linkage marker for the putative athero-genic gene in Chinese.

关 键 词：载脂蛋白 DNA多态 单倍型 冠心病 

分 类 号：R541.402[医药卫生—心血管疾病]