Nguyen Thuy Thu, Ho Tu Cam, Bui Huong Thi Thu, Tran Van-Khanh, Nguyen Tue Trong
Center for Gene and Protein Research, Hanoi Medical University, Hanoi 116177, Viet Nam.
Institute of Virology, TUM School of Medicine, Technical University of Munich, Munich 81675, Germany.
World J Gastroenterol. 2024 Dec 14;30(46):4880-4903. doi: 10.3748/wjg.v30.i46.4880.
Human leukocyte antigen (HLA) class II molecules are cell surface receptor proteins found on antigen-presenting cells. Polymorphisms and mutations in the gene can affect the immune system and the progression of hepatitis B.
To study the relation between rs2856718 of , rs3077, and rs9277535 of , hepatitis B virus (HBV)-related cirrhosis, and hepatocellular carcinoma (HCC).
In this case-control study, the genotypes of these single nucleotide polymorphisms (SNPs) were screened in 315 healthy controls, 471 chronic hepatitis B patients, 250 patients with HBV-related liver cirrhosis, and 251 patients with HCC using TaqMan real-time PCR. We conducted Hardy-Weinberg equilibrium and linkage disequilibrium tests on the genotype distributions of rs2856718, rs3077, and rs9277535 before hierarchical clustering analysis to build the complex interaction between the markers in each patient group.
The physical distance separating these SNPs was 29816 kB with the disequilibrium (D') values ranging from 0.07 to 0.34. The close linkage between rs3077 and rs9277535 was attributed to a distance of 21 kB. The D' value decreased from moderate in the healthy control group (D' = 0.50, < 0.05) to weak in the hepatic disease group (D' < 0.3, < 0.05). In a combination of the three variants rs2856718, rs3077, and rs9277535, the A allele decreased hepatic disease risk [A-A-A haplotype, risk ratio (RR) = 0.44 (0.14; 1.37), < 0.05]. The G allele had the opposite effect [G-A/G-G haplotype, RR = 1.12 (1.02; 1.23), < 0.05]. In liver cancer cases, the A-A-A/G haplotype increased the risk of HCC by 1.58 ( < 0.05).
Rs9277535 affects liver fibrosis progression due to HBV infection, while rs3077 is associated with a risk of HBV-related HCC. The link between rs2856718, rs3077, and rs9277535 and disease risk was determined using a multi-clustering analysis.
人类白细胞抗原（HLA）II类分子是在抗原呈递细胞上发现的细胞表面受体蛋白。该基因的多态性和突变会影响免疫系统以及乙型肝炎的进展。
研究[具体基因名称]的rs2856718、rs3077和rs9277535与乙型肝炎病毒（HBV）相关肝硬化和肝细胞癌（HCC）之间的关系。
在这项病例对照研究中，使用TaqMan实时荧光定量PCR技术对315名健康对照者、471名慢性乙型肝炎患者、250名HBV相关肝硬化患者和251名HCC患者进行这些单核苷酸多态性（SNP）的基因分型。在进行分层聚类分析以构建每个患者组中标记物之间的复杂相互作用之前，我们对rs2856718、rs3077和rs9277535的基因型分布进行了哈迪 - 温伯格平衡和连锁不平衡测试。
这些SNP之间的物理距离为29816 kB，不平衡（D'）值范围为0.07至0.34。rs3077和rs9277535之间的紧密连锁归因于21 kB的距离。D'值从健康对照组中的中度（D' = 0.50，P < 0.05）降至肝病组中的弱度（D' < 0.3，P < 0.05）。在rs2856718、rs3077和rs9277535这三个变体的组合中，A等位基因降低了肝病风险[A - A - A单倍型，风险比（RR）= 0.44（0.14；1.37），P < 0.05]。G等位基因则有相反的作用[G - A/G - G单倍型，RR = 1.12（1.02；1.23），P < 0.05]。在肝癌病例中，A - A - A/G单倍型使HCC风险增加1.58倍（P < 0.05）。
Rs9277535影响HBV感染导致的肝纤维化进展，而rs3077与HBV相关HCC的风险有关。使用多聚类分析确定了rs2856718、rs3077和rs9277535与疾病风险之间的联系。
