POLYMORPHISM IN THE HUMAN APOLIPOPROTEIN-A-I GENE PROMOTER REGION - ASSOCIATION OF THE MINOR ALLELE WITH DECREASED PRODUCTION-RATE INVIVO AND PROMOTER ACTIVITY INVITRO
POLYMORPHISM IN THE HUMAN APOLIPOPROTEIN-A-I GENE PROMOTER REGION - ASSOCIATION OF THE MINOR ALLELE WITH DECREASED PRODUCTION-RATE INVIVO AND PROMOTER ACTIVITY INVITRO
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DOI：
10.1172/jci115783
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发表时间：
1992-06-01
影响因子：
15.9
通讯作者：
BRESLOW, JL
中科院分区：
文献类型：
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作者：
SMITH, JD;BRINTON, EA;BRESLOW, JL
我们调查了一个常见的多态性在人载脂蛋白A-I基因启动子的转录起始位点上游76 bp的位置。54人受试者，其载脂蛋白AI生产率已确定的载脂蛋白AI营业额的研究，基因分型在这个多态性的位置，通过一种新的技术，使用聚合酶链反应，然后引物延伸。35例受试者在该基因座上为鸟苷（G）纯合型，19例为鸟苷和腺苷（A）杂合型。G/A杂合子的apoAI产生率显著低于G纯合子（P = 0.025），差异有统计学意义（P <0.05）。尽管apoAI基因启动子多态性对apoAI产生率有明显影响，但对HDL胆固醇或apoAI水平没有影响。为了研究所观察到的apoAI生产率的差异是否与两个等位基因的差异基因表达有关，将含有任一等位基因的启动子与报告基因氯霉素乙酰转移酶连接，并在转染到人HepG 2肝癌细胞系后测定相对启动子效率。A等位基因和G等位基因仅表达68%+/-5%，结果与体内apoAI产生速率数据一致。
We investigated a common polymorphism in the human apolipoprotein A-I gene promoter at a position 76 bp upstream of the transcriptional start site. 54 human subjects, whose apoAI production rates had been determined by apoAI turnover studies, were genotyped at this polymorphic position by a novel technique using polymerase chain reaction followed by primer extension. 35 subjects were homozygous for a guanosine (G) at this locus and 19 were heterozygous with a guanosine and adenosine (A). The apoAI production rates were significantly lower (by 11%) in the G/A heterozygotes than in the G homozygotes (P = 0.025). In spite of the apparent effect of this apoAI gene promoter polymorphism on the apoAI production rate, there was no effect on HDL cholesterol or apoAI levels. To investigate whether the observed difference in apoAI production rates was related to differential gene expression of the two alleles, promoters containing either allele were linked to the reporter gene chloramphenicol acetyltransferase, and relative promoter efficiencies were determined after transfection into the human HepG2 hepatoma cell line. The A allele expressed only 68%+/-5% as well as the G allele, a result consistent with the in vivo apoAI production rate data.