Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Sci Rep. 2019 May 3;9(1):6868. doi: 10.1038/s41598-019-43376-3.
Hepatocellular carcinoma (HCC) is a major health concern in Egypt owing to the high prevalence of hepatitis C virus (HCV) infection. HCC incidence is characterized by obvious male predominance, yet the molecular mechanisms behind this gender bias are still unidentified. Functional variations in X-linked genes have more impact on males than females. Glypican-3 (GPC3) gene, located in the Xq26 region, has lately emerged as being potentially implicated in hepatocellular carcinogenesis. The current study was designed to examine the association of -784 G/C single nucleotide polymorphism (SNP) in GPC3 promoter region (rs2267531) with HCC susceptibility in male and female Egyptian HCV patients. Our results revealed a significant association between GPC3 and HCC risk in both males and females, evidenced by higher C allele and CC/C genotype frequencies in HCC patients when compared to controls. However, no such association was found when comparing HCV patients to controls. Moreover, GPC3 gene and protein expression levels were significantly higher in CC/C than in GG/G genotype carriers in males and females. The CC/C genotype exhibited a significant shorter overall survival than GG/G genotype in HCC patients. In conclusion, GPC3 rs2267531 on the X chromosome is significantly associated with HCC, but not with HCV infection, in the Egyptian population.
肝细胞癌 (HCC) 在埃及是一个主要的健康关注点，这是由于丙型肝炎病毒 (HCV) 感染的高流行率所致。HCC 的发病率具有明显的男性优势，但导致这种性别偏见的分子机制仍未确定。X 连锁基因的功能变异对男性的影响大于女性。位于 Xq26 区域的 GPC3 基因（glypican-3）最近被认为可能与肝细胞癌的发生有关。本研究旨在探讨 GPC3 启动子区域（rs2267531）-784 G/C 单核苷酸多态性 (SNP) 与埃及男性和女性 HCV 患者 HCC 易感性的关系。我们的研究结果表明，GPC3 与 HCC 风险在男性和女性中均存在显著相关性，与对照组相比，HCC 患者的 C 等位基因和 CC/C 基因型频率更高。然而，在将 HCV 患者与对照组进行比较时，并未发现这种相关性。此外，在男性和女性中，CC/C 基因型携带者的 GPC3 基因和蛋白表达水平均显著高于 GG/G 基因型携带者。与 GG/G 基因型携带者相比，CC/C 基因型携带者的 HCC 患者总生存期明显缩短。总之，X 染色体上的 GPC3 rs2267531 与埃及人群的 HCC 显著相关，但与 HCV 感染无关。
