Motawi T, Shaker O G, Hussein R M, Houssen M
Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Balkan J Med Genet. 2017 Mar 9;19(2):35-44. doi: 10.1515/bjmg-2016-0034. eCollection 2016 Dec 1.
Hepatitis C virus (HCV) infection represents a serious health problem. The -174 G/C mutation in the pro inflammatory cytokine interleukin-6 (IL-6) is associated with developing liver diseases. Likewise, the S and Z mutations in the serine protease inhibitor α1-antitrypsin (A1AT) are associated with pulmonary emphysema and/or liver cirrhosis. We explored the distribution of the single nucleotide polymorphisms (SNPs) of and genes in chronic HCV-infected patients and evaluated their impact on the progression of liver cirrhosis. One hundred and fifty Egyptian HCV-infected patients together with 100 healthy controls were enrolled in this study. The patient groups were subdivided into chronic hepatitis patients ( = 85) and cirrhotic patients ( = 65). The SNP of IL-6 (-174 G/C, rs1800795), A1AT Z mutation (342 Glu/Lys, rs28929474) and A1AT S mutation (264 Glu/Val, rs17580) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Cirrhotic patients exhibited significantly increased frequency of the A1AT S allele compared with the controls (34.6 . 5.0%), while the chronic hepatitis patients showed a higher frequency of the A1AT Z allele compared with the controls (14.7 . 2.5%). Remarkably, IL-6 (CC genotype) was detected only in the chronic hepatitis patients. Multivariate regression analysis showed that aspartate transaminase (AST) and the S alleles of A1AT, represented as SS+MS genotypes, were significantly independent predictors for development of liver cirrhosis. We concluded that inheritance of deficient S and Z alleles of the gene but not IL-6 (-174 G/C), were associated with progressive liver diseases.
丙型肝炎病毒（HCV）感染是一个严重的健康问题。促炎细胞因子白细胞介素-6（IL-6）中的-174 G/C突变与肝脏疾病的发生有关。同样，丝氨酸蛋白酶抑制剂α1-抗胰蛋白酶（A1AT）中的S和Z突变与肺气肿和/或肝硬化有关。我们探讨了慢性HCV感染患者中IL-6和A1AT基因单核苷酸多态性（SNP）的分布，并评估了它们对肝硬化进展的影响。本研究纳入了150例埃及HCV感染患者和100例健康对照。患者组分为慢性肝炎患者（n = 85）和肝硬化患者（n = 65）。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法测定IL-6（-174 G/C，rs1800795）、A1AT Z突变（342 Glu/Lys，rs28929474）和A1AT S突变（264 Glu/Val，rs17580）的SNP。与对照组相比，肝硬化患者中A1AT S等位基因的频率显著增加（34.6%对5.0%），而慢性肝炎患者中A1AT Z等位基因的频率高于对照组（14.7%对2.5%）。值得注意的是，仅在慢性肝炎患者中检测到IL-6（CC基因型）。多因素回归分析表明，天冬氨酸转氨酶（AST）和A1AT的S等位基因（以SS + MS基因型表示）是肝硬化发生的显著独立预测因素。我们得出结论，A1AT基因的S和Z缺陷等位基因的遗传而非IL-6（-174 G/C）与进行性肝脏疾病有关。
