Tai Dar-In, Jeng Wen-Juei, Lin Chun-Yen
Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Linkou Medical Center Taoyuan City Taiwan.
Hepatol Commun. 2017 Nov 6;1(10):1005-1013. doi: 10.1002/hep4.1113. eCollection 2017 Dec.
Genome-wide association studies have indicated that human leukocyte antigen (HLA)-DP and HLA-DQ play roles in persistent hepatitis B virus (HBV) infection in Asia. To understand the evolution of HBV-related single nucleotide polymorphisms (SNPs) and to correlate these SNPs with chronic HBV infection among different populations, we conducted a global perspective study on hepatitis-related SNPs. We selected 12 HBV-related SNPs on the HLA locus and two HBV and three hepatitis C virus immune-related SNPs for analysis. Five nasopharyngeal carcinoma-related SNPs served as controls. All SNP data worldwide from 26 populations were downloaded from 1,000 genomes. We found a dramatic difference in the allele frequency in most of the HBV- and HLA-related SNPs in East Asia compared to the other continents. A sharp change in allele frequency in 8 of 12 SNPs was found between Bengali populations in Bangladesh and Chinese Dai populations in Xishuangbanna, China ( 0.001); these areas represent the junction of South and East Asia. For the immune-related SNPs, significant changes were found after leaving Africa. Most of these genes shifted from higher expression genotypes in Africa to lower expression genotypes in either Europe or South Asia ( 0.001). During this two-stage adaptation, immunity adjusted toward a weak immune response, which could have been a survival strategy during human migration to East Asia. The prevalence of chronic HBV infection in Africa is as high as in Asia; however, the HBV-related SNP genotypes are not present in Africa, and so the genetic mechanism of chronic HBV infection in Africa needs further exploration. Two stages of genetic changes toward a weak immune response occurred when humans migrated out of Africa. These changes could be a survival strategy for avoiding cytokine storms and surviving in new environments. ( 2017;1:1005-1013).
全基因组关联研究表明，人类白细胞抗原（HLA）-DP和HLA-DQ在亚洲持续性乙型肝炎病毒（HBV）感染中发挥作用。为了解HBV相关单核苷酸多态性（SNP）的演变，并将这些SNP与不同人群中的慢性HBV感染相关联，我们对肝炎相关SNP进行了一项全球视角研究。我们在HLA基因座上选择了12个HBV相关SNP以及2个HBV和3个丙型肝炎病毒免疫相关SNP进行分析。5个鼻咽癌相关SNP作为对照。从千人基因组计划下载了全球26个群体的所有SNP数据。我们发现，与其他各大洲相比，东亚大多数HBV和HLA相关SNP的等位基因频率存在显著差异。在孟加拉国的孟加拉人群体与中国西双版纳的傣族人群体之间，12个SNP中有8个的等位基因频率发生了急剧变化（P<0.001）；这些地区代表了南亚和东亚的交界处。对于免疫相关SNP，离开非洲后发现了显著变化。这些基因中的大多数从非洲的高表达基因型转变为欧洲或南亚的低表达基因型（P<0.001）。在这两个阶段的适应过程中，免疫力朝着弱免疫反应进行调整，这可能是人类向东亚迁移过程中的一种生存策略。非洲慢性HBV感染的患病率与亚洲一样高；然而，非洲不存在HBV相关SNP基因型，因此非洲慢性HBV感染的遗传机制需要进一步探索。当人类迁出非洲时，发生了两个阶段的向弱免疫反应的基因变化。这些变化可能是避免细胞因子风暴并在新环境中生存的一种生存策略。（2017；1：1005 - 1013）
