T-138C polymorphism of matrix gla protein promoter alters its expression but is not directly associated with atherosclerotic vascular calcification.
T-138C polymorphism of matrix gla protein promoter alters its expression but is not directly associated with atherosclerotic vascular calcification.
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发表时间：
2004
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通讯作者：
Noriyasu Kobayashi;R. Kitazawa;S. Maeda;L. Schurgers;S. Kitazawa
中科院分区：
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作者：
Noriyasu Kobayashi;R. Kitazawa;S. Maeda;L. Schurgers;S. Kitazawa
基质玻璃蛋白（MGP）是血管和软骨钙化的重要抑制剂。我们研究了T-138C MGP启动子多态性与动脉粥样硬化程度、血管钙化程度以及患者的临床背景（包括气管和肋软骨钙化）的关系。对108例尸体解剖标本进行了福尔马林固定石蜡包埋标本的多态性特异性PCR分析。多变量分析8个危险因素和5个与动脉粥样硬化和骨组织钙化相关的标志物之间的统计学相关性。我们发现因子与标记物之间存在非常高的典型相关，Pearson相关分析显示年龄与Gore指数之间存在6个显著相关；年龄与肋软骨钙化；性别与肋软骨钙化；高血压和戈尔指数；高血压与戈尔指数钙化因子的关系；以及高脂血症和肋软骨钙化。-138T等位基因启动子活性显著高于-138C等位基因；12- o -十四烷酚13-乙酸酯（TPA）处理对前者有显著的激活作用，而对后者几乎没有影响。与荷兰、北爱尔兰和法国相比，C基因型在日本受试者中更为常见（TT为45.5%，TC为37.6%，CC为16.8%）。然而，T-138C MGP启动子多态性与标记之间没有显著相关性。虽然C基因型（TC+CC）的钙化因子倾向于高于TT基因型，但戈尔指数和钙化因子在基因型之间无显著差异。虽然MGP启动子活性和AP-1转录因子的结合在体外实验中T-138和C-138 MGP启动子多态性有明显差异，但从统计学上看，T-138C多态性并不是腹主动脉动脉粥样硬化或动脉粥样硬化性血管钙化的独立因素。
Matrix Gla protein (MGP) is a crucial inhibitor of vessel and cartilage calcification. We investigated the association of T-138C MGP promoter polymorphism with the degree of atherosclerosis, vascular calcification and patients' clinical background including calcification of the trachea and costal cartilage. Analysis of 108 autopsy cases was carried out by polymorphism-specific PCR on formalin-fixed paraffin-embedded samples. Statistical correlations among eight risk factors and five markers related to atherosclerosis and extra-bone tissue calcification were multivariantly analyzed. We found very high canonical correlations between the factors and the markers, and Pearson's correlation analysis revealed six significant correlations between age and the Gore index; age and costal cartilage calcification; sex and costal cartilage calcification; hypertension and the Gore index; hypertension and the calcification factor of the Gore index; and hyperlipidemia and costal cartilage calcification. The promoter activity of the -138T allele was significantly higher than that of the -138C allele; treatment with 12-O-tetradecanonylphorbol 13-acetate (TPA) significantly activated the former, but had almost no effect on the latter. The C genotype was significantly common among Japanese subjects, (TT 45.5%, TC 37.6% and CC 16.8%) compared with that reported in the Netherlands, Northern Ireland and France. No significant correlation was observed, however, between T-138C MGP promoter polymorphism and the markers. Although the C genotype (TC+CC) tended to show a higher calcification factor than the TT genotype, no significant difference was observed among the genotypes in the Gore index or in the calcification factor. Although MGP promoter activity and the binding of the AP-1 transcription factor were clearly different between T-138 and C-138 MGP promoter polymorphism in vitro, T-138C polymorphism was, statistically, not an independent factor of atherosclerosis or atherosclerotic vascular calcification in the abdominal aorta.