Association of genetic variation in IL28B rs12979860 with development of hepatocellular carcinoma

Abu Saleh Mohammad Sadequl Islam, M. Mahtab, A. A. Mamun, M. F. Karim, S. M. Akbar, Mohammad Ali, Humayun Sattar, S. Rahman
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Abstract

The highest incidence of hepatocellular carcinoma (HCC) is in Asia, accounting for about 76% of all cases worldwide. In South East Asia, hepatitis B is the most common underlying cause. Although numerous associations between environmental factors (e.g. cigarette smoking, heavy alcohol drinking, male gender, older age), viral factors (e.g. viral load, active replication, genotype, core promoter mutations) and the development of HCC in chronic HBV infection have been identified, a clear understanding of the role of host genetics remains elusive. Bangladesh is a densely populated country with about 160 million populations, where HBsAg positivity in the healthy population is 5.4%. To evaluate the role of host IL28B (interleukin 28B; interferon lambda 3) single nucleotide polymorphism (SNP) in predicting hepatitis B virus (HBV)-related HCC susceptibility. Single SNP in the IL28B gene (rs12979860C/T) were examined in 116 subjects (including 44 HBVrelated HCC patients, 42 non-HCC patients with chronic hepatitis B and 30 healthy controls). The study was done at the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from January 2012 to December 2013.The polymorphism of IL28B rs12979860 was analyzed by a genotyping technique, based on polymerase chain reaction (PCR) followed by restriction enzyme analysis at the Department of Microbiology & Immunology, BSMMU. The frequency of CC homozygosity was 70% in healthy controls and 45.5% in HCC, the difference being statistically significant (χ2=4.35, P=0.03). Statistically significant difference was also seen between non-HCC patients with chronic hepatitis B (CHB) (69%) and HCC (45.5%) (χ2=4.35, P=0.03). However, this significant finding was not seen between non-HCC patients with chronic hepatitis B (CHB) and healthy controls. Carriers of the minor T allele in rs12979860 had a higher risk of HCC compared with non-carriers (χ2=4.78, P=0.02). Our results suggest that, T allele and non-CC genotypes have strong predictive effect of developing HCC and IL28Brs 12979860 C/T polymorphism might influence susceptibility to HCC.
IL28B rs12979860基因变异与肝癌发生的关系
肝细胞癌(HCC)发病率最高的地区是亚洲,约占全球所有病例的76%。在东南亚,乙型肝炎是最常见的潜在病因。虽然环境因素(如吸烟、大量饮酒、男性、年龄较大)、病毒因素(如病毒载量、活跃复制、基因型、核心启动子突变)与慢性HBV感染中HCC的发生之间存在许多关联,但对宿主遗传学的作用仍有明确的认识。孟加拉国是一个人口稠密的国家,约有1.6亿人口,健康人群中HBsAg阳性为5.4%。评价宿主白细胞介素28B (IL28B)的作用;干扰素lambda 3单核苷酸多态性(SNP)预测乙型肝炎病毒(HBV)相关HCC易感性的研究116例受试者(包括44例hbv相关HCC患者、42例慢性乙型肝炎非HCC患者和30例健康对照)检测IL28B基因单SNP (rs12979860C/T)。该研究于2012年1月至2013年12月在达卡Bangabandhu Sheikh Mujib医科大学(BSMMU)肝病学系完成。采用聚合酶链反应(PCR)和限制性内切酶(限制性内切酶)分析的方法,对IL28B rs12979860基因多态性进行了分型分析。健康对照组CC纯合率为70%,HCC组为45.5%,差异有统计学意义(χ2=4.35, P=0.03)。非HCC合并慢性乙型肝炎(CHB)患者(69%)与HCC合并慢性乙型肝炎(45.5%)患者(χ2=4.35, P=0.03)差异有统计学意义。然而,在非hcc合并慢性乙型肝炎(CHB)的患者和健康对照者之间没有发现这一重大发现。携带rs12979860中次要T等位基因的人群发生HCC的风险高于非携带者(χ2=4.78, P=0.02)。我们的研究结果表明,T等位基因和非cc基因型对肝癌的发生具有较强的预测作用,IL28Brs 12979860 C/T多态性可能影响肝癌的易感性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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