Cambien F, Ricard S, Troesch A, Mallet C, Générénaz L, Evans A, Arveiler D, Luc G, Ruidavets J B, Poirier O
INSERM SC7, Paris, France.
Hypertension. 1996 Nov;28(5):881-7. doi: 10.1161/01.hyp.28.5.881.
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 Leu10-->Pro, Arg25-->Pro; and 1 in the region of the gene coding for the precursor part of the protein not present in the active form, Thr263-->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 Pro25 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 Pro25 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 heterozygotes for Pro25 than in hormozygotes for Arg25 (odds ratio, 0.43, 95% confidence interval, 0.19 to 0.92; P < .03). Since the Pro25 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.
转化生长因子-β1（TGF-β1）在调节细胞生长与分化以及细胞外基质的产生和降解过程中发挥着重要作用。多项实验结果表明，TGF-β1可能参与心血管生理病理学过程。在本研究中，我们评估了TGF-β1基因是否为冠心病或高血压的候选基因。我们筛查了TGF-β基因编码区及其上游2181 bp区域的多态性，共鉴定出7个多态性位点：基因上游区域距首个转录核苷酸-988、-800和-509位置处有3个；非翻译区+72位置处有1个；信号肽序列Leu10→Pro、Arg25→Pro处有2个；以及基因编码蛋白前体部分（活性形式中不存在）的Thr263→Ile区域有1个。我们分析了来自北爱尔兰和法国四个地区的563例心肌梗死患者和629例对照受试者的这些TGF-β1多态性。在贝尔法斯特（P <.01）和斯特拉斯堡（P <.05），患者中Pro25等位基因的频率高于对照受试者。TGF-β1多态性与患者血管造影评估的冠状动脉疾病程度无关。Pro25等位基因的存在与四个对照组的较低收缩压相关（P <.002），Pro25纯合子或杂合子患高血压的病史明显少于Arg25纯合子（优势比，0.43，95%置信区间，0.19至0.92；P <.03）。由于Pro25等位基因与心肌梗死风险增加和高血压风险降低相关，我们倾向于谨慎解读这些明显不一致的结果。其他研究需要验证这些关联是否真实。
