Chou Hsiang-Tai, Chen Chien-Hsiun, Tsai Chang-Hai, Tsai Fuu-Jen
Division of Cardiology, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.
Am Heart J. 2004 Jul;148(1):181-6. doi: 10.1016/j.ahj.2004.03.032.
Scarring and collagen deposition in the valves and destruction of myocytes may result from the combined effects of a smoldering rheumatic process and a constant trauma to the mitral valve or aortic valve by the turbulent flow in rheumatic heart disease (RHD). Transforming growth factor-beta1 (TGF-beta1) may be responsible for the increased valvular fibrosis and calcification in the pathogenesis of RHD. However, the role of TGF-beta1 genetic variant in RHD has not been studied. This case-controlled study was carried out to investigate the possible relationship between the TGF-beta1 gene C-509T and T869C polymorphisms and RHD among the Chinese population in Taiwan.
A group of 115 patients with RHD documented by using echocardiography and 100 age- and sex-matched healthy control patients were studied. TGF-beta1 gene C-509T and T869C polymorphisms were identified with polymerase chain reaction-based restriction analysis.
A significant difference was seen in the distribution of genotypes between patients with RHD and control patients for either TGF-beta1 C-509T polymorphism (P <.0001) or T869C polymorphism (P <.0001). The frequency of TGF-beta1 C-509T CC genotype was lower in the RHD group than in the control group (chi2 = 19.05, P <.0001), which suggests that this genotype may confer protective effects against RHD. A significant difference was seen in the distribution of allelic frequency between patients with RHD and control patients for TGF-beta1 T869C polymorphism (P =.04). The odds ratio (OR) for risk of RHD associated with TGF-beta1 T869C T allele was 1.49 (95% CI, 1.02-2.19). Further categorization of patients with RHD into mitral valve disease and combined valve disease subgroups revealed no statistical difference in these gene polymorphisms when compared with the 2 subgroups.
Patients with RHD have a lower frequency of TGF-beta1 C-509T CC genotype and a higher frequency of T869C T allele, which supports a role for the TGF-beta1 gene C-509T and T869C polymorphisms in determining the risk/protection of RHD in Taiwan Chinese patients.
风湿性心脏病（RHD）中，隐匿性风湿过程与二尖瓣或主动脉瓣因湍流产生的持续创伤共同作用，可能导致瓣膜瘢痕形成、胶原蛋白沉积及心肌细胞破坏。转化生长因子β1（TGF-β1）可能在RHD发病机制中导致瓣膜纤维化和钙化增加。然而，TGF-β1基因变异在RHD中的作用尚未得到研究。本病例对照研究旨在探讨台湾地区中国人群中TGF-β1基因C-509T和T869C多态性与RHD之间的可能关系。
研究了一组经超声心动图确诊的115例RHD患者以及100例年龄和性别匹配的健康对照患者。采用基于聚合酶链反应的限制性分析鉴定TGF-β1基因C-509T和T869C多态性。
对于TGF-β1 C-509T多态性（P <.0001）或T869C多态性（P <.0001），RHD患者与对照患者的基因型分布存在显著差异。RHD组中TGF-β1 C-509T CC基因型的频率低于对照组（χ2 = 19.05，P <.0001），这表明该基因型可能对RHD具有保护作用。对于TGF-β1 T869C多态性，RHD患者与对照患者的等位基因频率分布存在显著差异（P =.04）。与TGF-β1 T869C T等位基因相关的RHD风险比值比（OR）为1.49（95% CI，1.02 - 2.19）。将RHD患者进一步分为二尖瓣疾病和联合瓣膜疾病亚组后，与这两个亚组相比，这些基因多态性无统计学差异。
RHD患者中TGF-β1 C-509T CC基因型频率较低，T869C T等位基因频率较高，这支持TGF-β1基因C-509T和T869C多态性在决定台湾地区中国患者RHD风险/保护方面发挥作用。
