PMID- 34164868
OWN - NLM
STAT- MEDLINE
DCOM- 20220307
LR  - 20221207
IS  - 1521-2254 (Electronic)
IS  - 1099-498X (Print)
IS  - 1099-498X (Linking)
VI  - 23
IP  - 11
DP  - 2021 Nov
TI  - Association between HLA alleles and Epstein-Barr virus Zta-IgA serological status 
      in healthy males from southern China.
PG  - e3375
LID - 10.1002/jgm.3375 [doi]
LID - e3375
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV) 
      associated cancer, exhibits an extremely high incidence in southern Chinese. 
      Given that human leukocyte antigen (HLA) plays critical roles in antigen 
      presentation and relates to NPC susceptibility, it is speculated that certain HLA 
      variants may affect EBV reactivation, which is a key pathogenic factor of NPC. 
      Therefore, we attempted to identify HLA alleles associated with the indicator of 
      EBV reactivation, Zta-IgA, in healthy males from NPC endemic area. METHODS: HLA 
      alleles of 1078 healthy males in southern China from the 21-RCCP study were 
      imputed using genome-wide single nucleotide polymorphism data. EBV Zta-IgA in 
      blood samples were measured using an enzyme-linked immunosorbent assay. Multiple 
      logistic regression analysis was used to evaluate the effect of HLA allele on 
      Zta-IgA serological status and its potential joint association with smoking. The 
      binding affinity for Zta-peptide was predicted using NetMHCIIpan 4.0. RESULTS: 
      HLA-DRB1*09:01 was found to be associated with a higher risk of Zta-IgA 
      seropositivity (odds ratio = 1.80, 95% confidence interval = 1.32-2.45; 
      p = 1.82 x 10(-4) ). Compared with non-smokers without HLA-DRB1*09:01, the effect 
      size increased to 2.19- and 3.70-fold for the light and heavy smokers carrying 
      HLA-DRB1*09:01, respectively. Furthermore, HLA-DRB1*09:01 showed a stronger 
      binding affinity to Zta peptide than other HLA-DRB1 alleles. CONCLUSIONS: Our 
      study highlighted the pivotal role of genetic HLA variants in EBV reactivation 
      and the etiology of NPC. Smokers with HLA-DRB1*09:01 have a significantly higher 
      risk of being Zta-IgA seropositive, which indicates the necessity of smoking 
      cessation in certain high-risk populations and also provide clues for further 
      research on the etiology of NPC.
CI  - (c) 2021 The Authors. The Journal of Gene Medicine published by John Wiley & Sons 
      Ltd.
FAU - Yuan, Lei-Lei
AU  - Yuan LL
AD  - School of Public Health, Sun Yat-sen University, Guangzhou, China.
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Deng, Chang-Mi
AU  - Deng CM
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Xue, Wen-Qiong
AU  - Xue WQ
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - He, Yong-Qiao
AU  - He YQ
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Wang, Tong-Min
AU  - Wang TM
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Zhang, Jiang-Bo
AU  - Zhang JB
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Yang, Da-Wei
AU  - Yang DW
AD  - School of Public Health, Sun Yat-sen University, Guangzhou, China.
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Zhou, Ting
AU  - Zhou T
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Wu, Zi-Yi
AU  - Wu ZY
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Liao, Ying
AU  - Liao Y
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Zheng, Mei-Qi
AU  - Zheng MQ
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Li, Dan-Hua
AU  - Li DH
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Cao, Lian-Jing
AU  - Cao LJ
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Jia, Yi-Jing
AU  - Jia YJ
AD  - School of Public Health, Sun Yat-sen University, Guangzhou, China.
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Zhang, Wen-Li
AU  - Zhang WL
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Xiao, Ruo-Wen
AU  - Xiao RW
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Luo, Lu-Ting
AU  - Luo LT
AD  - School of Public Health, Sun Yat-sen University, Guangzhou, China.
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Tong, Xia-Ting
AU  - Tong XT
AD  - School of Public Health, Sun Yat-sen University, Guangzhou, China.
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Wu, Yan-Xia
AU  - Wu YX
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Huang, Jing-Wen
AU  - Huang JW
AD  - School of Public Health, Sun Yat-sen University, Guangzhou, China.
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Jia, Wei-Hua
AU  - Jia WH
AUID- ORCID: 0000-0002-0528-8715
AD  - School of Public Health, Sun Yat-sen University, Guangzhou, China.
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210706
PL  - England
TA  - J Gene Med
JT  - The journal of gene medicine
JID - 9815764
RN  - 0 (Antibodies, Viral)
RN  - 0 (BZLF1 protein, Herpesvirus 4, Human)
RN  - 0 (HLA Antigens)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Trans-Activators)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Antibodies, Viral/immunology
MH  - Asian People/genetics
MH  - Epstein-Barr Virus Infections/*immunology/virology
MH  - Genome-Wide Association Study/methods
MH  - Genotype
MH  - HLA Antigens/*genetics
MH  - Healthy Volunteers
MH  - Herpesvirus 4, Human/*immunology
MH  - Humans
MH  - Immunoglobulin A/blood/*immunology
MH  - Male
MH  - Middle Aged
MH  - Nasopharyngeal Carcinoma/*genetics/*immunology
MH  - Nasopharyngeal Neoplasms/genetics/immunology
MH  - Smoking/adverse effects
MH  - Trans-Activators/*immunology
MH  - Viral Proteins/immunology
PMC - PMC8596395
OTO - NOTNLM
OT  - Epstein-Barr virus
OT  - Zta-IgA
OT  - human leukocyte antigen
OT  - nasopharyngeal carcinoma
OT  - smoking
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2021/06/25 06:00
MHDA- 2022/03/08 06:00
PMCR- 2021/11/17
CRDT- 2021/06/24 06:57
PHST- 2021/03/31 00:00 [received]
PHST- 2021/06/22 00:00 [accepted]
PHST- 2021/06/25 06:00 [pubmed]
PHST- 2022/03/08 06:00 [medline]
PHST- 2021/06/24 06:57 [entrez]
PHST- 2021/11/17 00:00 [pmc-release]
AID - JGM3375 [pii]
AID - 10.1002/jgm.3375 [doi]
PST - ppublish
SO  - J Gene Med. 2021 Nov;23(11):e3375. doi: 10.1002/jgm.3375. Epub 2021 Jul 6.