Samokhodskaia L M, Starostina E E, Yarovaya E B, Krasnova T N, Mukhin N A, Tkachuk V A, Sadovnichy V A
Vestn Ross Akad Med Nauk. 2015(6):651-61. doi: 10.15690/vramn548.
To evaluate clinical significance of different combinations of gene polymorphisms IL-1b, IL-6, IL-10, TNF, HFE, TGF-b, ATR1, N0S3894, CYBA, AGT, MTHFR, FII, FV, FVII, FXIII, ITGA2, ITGB3, FBG, PAI and their prognostic value for prediction of liver fibrosis progression rate in patients with chronic hepatitis C (CHC).
118 patients with CHC were divided into "fast" and "slow" (fibrosis rate progression ≥ 0.13 and < 0.13 fibrosis units/yr; n = 64 and n = 54) fibrosis groups. Gene polymorphisms were determined. Statistical analysis was performed using Statistica 10.
A allele (p = 0.012) and genotype AA (p = 0.024) of AGT G-6T gene, as well as T allele (p = 0.013) and MT+TT genotypes (p = 0.005) of AGT 235 M/T gene were significantly more common in "fast fibrosers" than in "slow fibrosers". Patients with genotype TT of CYBA 242 C/T had a higher fibrosis progression rate than patients with CC+CT genotype (p = 0.02). Our analysis showed a protective effect of TTgenotype of ITGA2 807 C/T on fibrosis progression rate (p = 0.03). There was a trend (p < 0.15) to higher fibrosis progression rate in patients with mutant alleles and genotypes of TGFb +915 G/C, FXIII 103 G/T, PAI-675 5G/4G genes. Other gene polymorphisms were not associated with enhanced liver fibrosis. To build a mathematical modelfor prediction of liverfibrosis progression rate we performed coding with scores for genotypes and virus genotype. Total score correlated with the fibrosis progression rate (R = 0.39, p = 0.000).
Determination of genetic profile of the patient and virus genotype allows to predict the course of CHC.
评估白细胞介素 -1β（IL-1b）、白细胞介素 -6（IL-6）、白细胞介素 -10（IL-10）、肿瘤坏死因子（TNF）、遗传性血色素沉着症基因（HFE）、转化生长因子 -β（TGF-b）、血管紧张素 II 受体 1（ATR1）、一氧化氮合酶 3 894（NOS3894）、细胞色素 b5 还原酶（CYBA）、血管紧张素原（AGT）、亚甲基四氢叶酸还原酶（MTHFR）、凝血因子 II（FII）、凝血因子 V（FV）、凝血因子 VII（FVII）、凝血因子 XIII（FXIII）、整合素α2（ITGA2）、整合素β3（ITGB3）、纤维蛋白原（FBG）、纤溶酶原激活物抑制剂（PAI）基因多态性的不同组合的临床意义及其对慢性丙型肝炎（CHC）患者肝纤维化进展率预测的预后价值。
118 例 CHC 患者被分为“快速”和“缓慢”（纤维化率进展≥0.13 和<0.13 纤维化单位/年；n = 64 和 n = 54）纤维化组。测定基因多态性。使用 Statistica 10 进行统计分析。
AGT G-6T 基因的 A 等位基因（p = 0.012）和 AA 基因型（p = 0.024），以及 AGT 235 M/T 基因的 T 等位基因（p = 0.013）和 MT + TT 基因型（p = 0.005）在“快速纤维化者”中比“缓慢纤维化者”显著更常见。CYBA 242 C/T 的 TT 基因型患者的纤维化进展率高于 CC + CT 基因型患者（p = 0.02）。我们的分析显示 ITGA2 807 C/T 的 TT 基因型对纤维化进展率有保护作用（p = 0.03）。TGFb +915 G/C、FXIII 103 G/T、PAI-675 5G/4G 基因的突变等位基因和基因型患者的纤维化进展率有升高趋势（p < 0.15）。其他基因多态性与肝纤维化增强无关。为建立肝纤维化进展率预测的数学模型，我们对基因型和病毒基因型进行了评分编码。总分与纤维化进展率相关（R = 0.39，p = 0.000）。
确定患者的基因谱和病毒基因型有助于预测 CHC 的病程。
