Human Leukocyte Antigen Genotypes Affect Hepatitis B Virus Mutations Associated With Hepatocellular Carcinoma.

IF 3.4 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Hepatology Research Pub Date : 2025-07-29 DOI:10.1111/hepr.70007

Masaya Sugiyama, Nao Nishida, Seik-Soon Khor, Tadasu Shin-I, Keisuke Hino, Masao Honda, Shuichi Kaneko, Hiroshi Yatsuhashi, Kazuhiko Koike, Masayuki Kurosaki, Namiki Izumi, Yasuhito Tanaka, Kazumoto Murata, Jong-Hon Kang, Eiji Tanaka, Akinobu Taketomi, Yuichiro Eguchi, Goki Suda, Naoya Sakamoto, Kazuhide Yamamoto, Akihiro Tamori, Shuhei Hige, Yoshito Itoh, Satoshi Mochida, Eiji Mita, Tatsuya Ide, Yoichi Hiasa, Masahiko Watanabe, Ken Yamamoto, Aiko Sakai, Takaji Wakita, Masashi Mizokami, Katsushi Tokunaga

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引用次数: 0

Abstract

Background and aims: Various viral mutations have been reported to influence disease pathogenesis in infectious diseases. However, these mutations may remain undetected due to patient population changes. Although many causes have been proposed, the exact reasons remain unclear. This study analyzed viral mutations linked to hepatocellular carcinoma (HCC) in patients with hepatitis B by comparing factors between condition-matched patient groups of different human leukocyte antigen (HLA) genotypes.

Methods: HLA genotypes of 2281 healthy individuals, 370 patients with hepatitis B virus (HBV)-derived HCC, and 408 patients with chronic hepatitis B were analyzed to identify HLA genotypes associated with HCC development. Patients with HCC were grouped by HLA-DPB1 genotype to identify HBV genomic variants linked to HCC.

Results: The HLA-DPB1*02:01, 04:01, and 04:02 alleles suppressed chronic hepatitis B (CHB) and HCC development (P = 4.53 × 10^-9, 3.20 × 10^-3, and 3.03 × 10^-4, respectively). Conversely, HLA-DPB1*05:01 and 09:01 alleles were significantly associated with CHB and HCC development (P = 1.01 × 10^-7, 6.51 × 10^-8, respectively). Among HLA-DPB1*02:01 patients, the S166L amino acid (AA) mutation in the PreS/S region of the HBV genome was significantly identified. HLA-DPB1*05:01 homozygous patients significantly had K130M/V131I AA mutations in the X region of the HBV genome, whereas HLA-DPB1*05:01-09:01 heterozygous patients significantly had the H94Y AA mutation in the X region. Stratification by HLA genotype changed the mutation position and strengthened the odds ratios for developing HCC due to viral mutations.

Conclusions: Our analysis revealed that viral mutations associated with HCC vary by HLA genotype. These findings suggest a host-pathogen genetic interaction. HLA genotype stratification may aid in advancing personalized genomic medicine, which has been challenging to apply to chronic diseases.

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人白细胞抗原基因型影响与肝细胞癌相关的乙型肝炎病毒突变

背景与目的：各种病毒突变已被报道影响传染病的发病机制。然而，由于患者群体的变化，这些突变可能仍未被发现。虽然提出了许多原因，但确切原因尚不清楚。本研究通过比较不同人类白细胞抗原（HLA）基因型条件匹配患者组之间的因素，分析了乙型肝炎患者中与肝细胞癌（HCC）相关的病毒突变。方法：对2281例健康人、370例乙型肝炎病毒（HBV）源性HCC患者和408例慢性乙型肝炎患者的HLA基因型进行分析，以确定HCC发生的相关HLA基因型。HCC患者按HLA-DPB1基因型分组，以确定与HCC相关的HBV基因组变异。结果：HLA-DPB1*02:01、04:01和04:02等位基因抑制慢性乙型肝炎（CHB）和HCC的发生（P值分别为4.53 × 10-9、3.20 × 10-3和3.03 × 10-4）。相反，HLA-DPB1*05:01和09:01等位基因与CHB和HCC的发展显著相关（P分别为1.01 × 10-7、6.51 × 10-8）。在HLA-DPB1*02:01患者中，HBV基因组PreS/S区S166L氨基酸（AA）突变显著。HLA-DPB1*05:01纯合子患者在HBV基因组X区显著存在K130M/V131I AA突变，而HLA-DPB1*05:01-09:01杂合子患者在X区显著存在H94Y AA突变。HLA基因型分层改变了突变位置，增强了因病毒突变而发生HCC的优势比。结论：我们的分析显示，与HCC相关的病毒突变因HLA基因型而异。这些发现表明存在宿主-病原体遗传相互作用。HLA基因型分层可能有助于推进个性化基因组医学，这在慢性疾病的应用方面一直具有挑战性。

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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来源期刊

Hepatology Research 医学-胃肠肝病学

CiteScore

8.30

自引率

14.30%

发文量

124

审稿时长

1 months

期刊介绍： Hepatology Research (formerly International Hepatology Communications) is the official journal of the Japan Society of Hepatology, and publishes original articles, reviews and short comunications dealing with hepatology. Reviews or mini-reviews are especially welcomed from those areas within hepatology undergoing rapid changes. Short communications should contain concise definitive information.