Polymorphisms of the transforming growth factor-beta 1 gene in relation to myocardial infarction and blood pressure - The Etude Cas-Temoin de l'Infarctus du Myocarde (ECTIM) Study
Polymorphisms of the transforming growth factor-beta 1 gene in relation to myocardial infarction and blood pressure - The Etude Cas-Temoin de l'Infarctus du Myocarde (ECTIM) Study
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DOI：
10.1161/01.hyp.28.5.881
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发表时间：
1996-11-01
期刊：
影响因子：
8.3
通讯作者：
Poirier, O
中科院分区：
文献类型：
--
作者：
Cambien, F;Ricard, S;Poirier, O
转化生长因子-β 1（TGF-β 1）在调节细胞生长和分化以及细胞外基质的产生和降解中起重要作用。许多实验结果表明，TGF-β 1可能参与心血管病理生理学。在本研究中，我们评估了TGF-β 1基因是否是冠心病或高血压的候选基因。我们对TGF-β基因编码区和上游2181 bp的多态性进行了筛选，发现了7个多态性：3个在基因上游区，从第一个转录核苷酸开始的-988，-800和-509位点，1个在非翻译区，+72位点，2个在信号肽序列Leu（10）->Pro，Arg（25）->Pro，3个在信号肽序列Leu（10）->Pro，Arg（25）->Pro。在编码不以活性形式存在的蛋白质的前体部分的基因区域中，Thr（263）->Ile。我们分析了来自北方爱尔兰和法国四个地区的563名心肌梗死患者和629名对照受试者的这些TGF-β 1多态性。pro（25）等位基因在贝尔法斯特（P <0.01）和斯特拉斯堡（P <0.05）患者中的频率高于对照组。TGF-β 1基因多态性与冠状动脉病变程度无关。在4个对照组中，Pro（25）等位基因的存在与较低的收缩压相关（P <0.002），Pro（25）纯合子或杂合子的高血压史显著低于Arg（25）纯合子（优势比，0.43; 95%可信区间，0.19 ~ 0.92; P <0.03）。由于pro（25）等位基因与心肌梗死风险增加和高血压风险降低相关，我们倾向于谨慎解释这些明显不一致的结果。其他的研究需要验证这些联系是否是真实的。
Transforming growth factor-beta 1 (TGF-beta 1) plays an important role in the modulation of cellular growth and differentiation and the production and degradation of the extracellular matrix. A number of experimental results suggest that TGF-beta 1 may be involved in cardiovascular physiopathology. In the present study, we assessed whether the TGF-beta 1 gene is a candidate gene for coronary heart disease or hypertension. We screened the coding region and 2181 bp upstream of the TGF-beta gene for polymorphisms and identified seven polymorphisms: 3 in the upstream region of the gene at positions -988, -800, and -509 from the first transcribed nucleotide; 1 in a nontranslated region at position +72; 2 in the signal peptide sequence Leu(10)-->Pro, Arg(25)-->Pro; and 1 in the region of the gene coding for the precursor part of the protein not present in the active form, Thr(263)-->Ile. We analyzed these TGF-beta 1 polymorphisms in 563 patients with myocardial infarction and 629 control subjects from four regions in Northern Ireland and France. The pro(25) allele was more frequent in patients than in control subjects in Belfast (P < .01) and Strasbourg (P < .05). The TGF-beta 1 polymorphisms were not associated with the degree of angiographically assessed coronary artery disease in patients. The presence of a Pro(25) allele was associated with a lower systolic pressure in the four control groups (P < .002), and a history of hypertension was significantly less frequent in homozygotes or heterozygores for pro(25) than in homozygotes for Arg(25) (odds ratio, 0.43; 95% confidence interval, 0.19 to 0.92; P < .03). Since the pro(25) allele was associated with an increased risk of myocardial infarction and a reduced risk of hypertension, we favor a cautious interpretation of these apparently inconsistent results. Other studies will need to verify whether these associations are real.