HLA Zygosity Increases Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma
HLA Zygosity Increases Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma
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DOI：
10.1093/infdis/jiab207
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发表时间：
2021-04-14
影响因子：
6.4
通讯作者：
Yang, Hwai-, I
中科院分区：
文献类型：
--
作者：
Liu, Zhiwei;Huang, Chih-Jen;Yang, Hwai-, I
背景HLA基因的多样性可能与疾病结局相关-杂合子优势假说。我们测试了这一假设与B肝炎病毒（HBV）相关的肝细胞癌（MCC）。我们利用来自超过10000名目前或过去有HBV感染的台湾个体的DNA来研究HLA多样性与HBV感染发展为HCC的关键自然史步骤之间的关联。当在一个位点上的2个HLA等位基因被插补为携带相同的4位数等位基因时，个体被归类为在该位点上的纯合子。纯合HLA II类基因座数量的增加与慢性HBV感染风险的增加相关（P趋势= 1.18 × 10 - 7）。在慢性HBV携带者中，纯合HLA II类基因座数量的增加也与HBV相关HCC风险的增加相关（P趋势= 0.031）。对于单个HLA基因座，HLA-DQB 1纯合性与HCC风险显著相关（校正风险比= 1.40; 95%置信区间，1.06-1.84）。我们还发现接合性通过其影响病毒控制的能力影响HCC的风险。HLA II类基因座的纯合性，特别是HLA-DQB 1，与HBV相关HCC的高风险相关。
Background. Diversity in the HLA genes might be associated with disease outcomes-the heterozygote advantage hypothesis. We tested this hypothesis in relation to hepatitis B virus (HBV)-associated hepatocellular carcinoma (MCC).Methods. We utilized DNA from > 10 000 Taiwanese individuals with current or past HBV infection to examine the association between HLA diversity and critical natural history steps in the progression from HBV infection to HCC. Individuals were classified as homozygotes at a given locus when imputed to carry the same 4-digit allele for the 2 HLA alleles at that locus.Results. Increase in number of homozygous HLA class II loci was associated with an increased risk of chronic HBV infection (P-trend = 1.18 x 10(-7)). Among chronic HBV carriers, increase in number of homozygous HLA class II loci was also associated with an increased risk of HBV-associated HCC (P-trend = .031). For individual HLA loci, HLA-DQB1 homozygosity was significantly associated with HCC risk (adjusted hazard ratio = 1.40; 95% confidence interval, 1.06-1.84). We also found that zygosity affects risk of HCC through its ability to affect viral control.Conclusions. Homozygosity at HLA class II loci, particularly HLA-DQB1, is associated with a higher risk of HBV-associated HCC.