Dai Chia-Yen, Chuang Wan-Long, Lee Li-Po, Pan Wen-Cheng, Huang Jee-Fu, Hsieh Ming-Yen, Hou Nai-Jen, Lin Zu-Yau, Chen Shinn-Cherng, Hsieh Ming-Yuh, Wang Liang-Yen, Chang Wen-Yu, Yu Ming-Lung
Hepatobiliary Division, Department of Internal Medicine, the Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Transl Res. 2008 Oct;152(4):151-6. doi: 10.1016/j.trsl.2008.08.001. Epub 2008 Sep 9.
The production of transforming growth factor beta 1 (TGF-beta1) has been reported as being significantly associated with the gene polymorphism in the leader sequence at positions +29. The current study aimed to evaluate the associations between the polymorphism and the clinical characteristics of chronic hepatitis C (CHC). A total of 422 (252 men; mean age: 49.7 +/- 11.2 years) Taiwanese CHC patients with liver biopsies were enrolled. The TGF-beta1 gene polymorphism at position +29 (T or C), hepatitis C virus (HCV) RNA genotypes, and serum HCV RNA levels of these patients were determined. Of the 422 patients, the frequency of the T allele was 45.4%. Based on univariate analyses, a significantly lesser proportion of patients with allele T had high viral loads than those who were without allele T (P = 0.026). The lesser HCV RNA levels and HCV genotype 1b infection were significantly associated with the inheritance of the T allele in female patients based on univariate (P = 0.012 and 0.007, respectively) and multivariate regression (odds ratio/95% confidence interval: 0.434/0.219-0.859 and 0.468/0.237-0.927, respectively) analyses. In male patients with or without inheritance of the T allele, the clinical characteristics were similar. In conclusion, the association between TGF-beta1 polymorphism and virologic characteristics of chronic HCV infection implicated a significant role of host genetic factors on the clinical features of CHC. Female patients who carry T allele at position +29 were predisposed to be associated with HCV genotype non-1b infection and lesser HCV viral load, which revealed the gender effect.
据报道,转化生长因子β1(TGF-β1)的产生与位于+29位的前导序列中的基因多态性显著相关。本研究旨在评估该多态性与慢性丙型肝炎(CHC)临床特征之间的关联。共纳入422例(252例男性;平均年龄:49.7±11.2岁)接受肝活检的台湾CHC患者。测定了这些患者在+29位的TGF-β1基因多态性(T或C)、丙型肝炎病毒(HCV)RNA基因型以及血清HCV RNA水平。在422例患者中,T等位基因的频率为45.4%。基于单因素分析,携带T等位基因的患者中病毒载量高的比例显著低于不携带T等位基因的患者(P = 0.026)。基于单因素(分别为P = 0.012和0.007)和多因素回归分析(优势比/95%置信区间:分别为0.434/0.219 - 0.859和0.468/0.237 - 0.927),较低的HCV RNA水平和HCV基因型1b感染与女性患者中T等位基因的遗传显著相关。在携带或不携带T等位基因遗传的男性患者中,临床特征相似。总之,TGF-β1多态性与慢性HCV感染的病毒学特征之间的关联表明宿主遗传因素在CHC临床特征中起重要作用。在+29位携带T等位基因的女性患者易发生HCV基因型非1b感染且HCV病毒载量较低,这显示了性别效应。