PMID- 35470498
OWN - NLM
STAT- MEDLINE
DCOM- 20220608
LR  - 20220716
IS  - 1098-2825 (Electronic)
IS  - 0887-8013 (Print)
IS  - 0887-8013 (Linking)
VI  - 36
IP  - 6
DP  - 2022 Jun
TI  - Genome-wide association study of 7661 Chinese Han individuals and fine-mapping 
      major histocompatibility complex identifies HLA-DRB1 as associated with IgA 
      vasculitis.
PG  - e24457
LID - 10.1002/jcla.24457 [doi]
LID - e24457
AB  - BACKGROUND: Immunoglobulin-A vasculitis (IgAV) is an immune-related systemic 
      vasculitis with an unclear etiology. Genetic predisposition is now considered to 
      be closely associated with the development of the disease, and it is essential to 
      reveal the relationship between them. To explore the role of heredity in the 
      disease, we performed a genome-wide association study (GWAS) of 496 IgAV cases 
      and 7165 controls using an Illumina Infinium Global Screening Array chip. 
      METHODS: In the first stage of analysis, a significant correlation between the 
      major histocompatibility complex (MHC) and IgAV was observed. Subsequently, human 
      leukocyte antigen (HLA) analysis was conducted using a new large-scale Han-MHC 
      reference panel. Fine mapping of IgAV risk in the MHC region indicated that two 
      amino acid positions, 120 and 11, of HLA-DRB1 and three potential HLA alleles 
      (HLA-DRB1 *04, HLA-DRB1 *16, and HLA-DRB1 *16:02) were significantly associated. 
      RESULTS: Further stepwise conditional analysis demonstrated that 3 amino acid 
      positions (120, 26, 96) of HLA-DRB1 and 6 HLA-DRB1 alleles (HLA-DRB1*04, 
      HLA-DRB1*16, HLA-DRB1*01, HLA-DRB1*12:02, HLA-DRB1*10, and HLA-DRB1*15:02) were 
      independent signals. Among them, the most significant signal was HLA-DRB1 amino 
      acid Ser120 (OR = 1.59, p = 3.19 x 10(-8) ); no independent signal in the MHC 
      region except for HLA-DRB1 was found. CONCLUSIONS: Our study confirms that the 
      pathogenesis of IgAV has a genetic component and that HLA-DRB1 is strongly 
      associated with susceptibility to IgAV.
CI  - (c) 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley 
      Periodicals LLC.
FAU - Xia, Liang
AU  - Xia L
AD  - Institute of Dermatology and Department of Dermatology of the First Affiliated 
      Hospital, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, 
      Hefei, China.
AD  - Department of Hematology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei, China.
FAU - Chen, Mengyun
AU  - Chen M
AD  - Institute of Dermatology and Department of Dermatology of the First Affiliated 
      Hospital, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, 
      Hefei, China.
FAU - Zhang, Hanshuo
AU  - Zhang H
AD  - Department of Hematology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei, China.
FAU - Zheng, Xiaodong
AU  - Zheng X
AD  - Institute of Dermatology and Department of Dermatology of the First Affiliated 
      Hospital, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, 
      Hefei, China.
FAU - Bao, Jing
AU  - Bao J
AD  - Department of Hematology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei, China.
FAU - Gao, Jinping
AU  - Gao J
AD  - Institute of Dermatology and Department of Dermatology of the First Affiliated 
      Hospital, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, 
      Hefei, China.
FAU - Zhu, Caihong
AU  - Zhu C
AD  - Institute of Dermatology and Department of Dermatology of the First Affiliated 
      Hospital, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, 
      Hefei, China.
FAU - Sun, Liangdan
AU  - Sun L
AD  - Institute of Dermatology and Department of Dermatology of the First Affiliated 
      Hospital, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, 
      Hefei, China.
FAU - Xia, Hailong
AU  - Xia H
AD  - Department of Hematology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei, China.
AD  - Department of Hematology, Chaohu Hospital, Anhui Medical University, Hefei, 
      China.
FAU - Zhang, Xuejun
AU  - Zhang X
AUID- ORCID: 0000-0002-7958-498X
AD  - Institute of Dermatology and Department of Dermatology of the First Affiliated 
      Hospital, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, 
      Hefei, China.
LA  - eng
GR  - 81320108016/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20220425
PL  - United States
TA  - J Clin Lab Anal
JT  - Journal of clinical laboratory analysis
JID - 8801384
RN  - 0 (Amino Acids)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Alleles
MH  - Amino Acids
MH  - China/epidemiology
MH  - Genetic Predisposition to Disease/genetics
MH  - *Genome-Wide Association Study
MH  - HLA-DRB1 Chains/genetics
MH  - Humans
MH  - *IgA Vasculitis
MH  - Major Histocompatibility Complex
PMC - PMC9169162
OTO - NOTNLM
OT  - HLA-DRB1
OT  - Henoch-Schonlein purpura
OT  - Immunoglobulin-A vasculitis
OT  - susceptibility
COIS- The authors declare that they have no competing interests.
EDAT- 2022/04/27 06:00
MHDA- 2022/06/09 06:00
PMCR- 2022/04/25
CRDT- 2022/04/26 06:00
PHST- 2022/03/21 00:00 [revised]
PHST- 2021/10/21 00:00 [received]
PHST- 2022/04/14 00:00 [accepted]
PHST- 2022/04/27 06:00 [pubmed]
PHST- 2022/06/09 06:00 [medline]
PHST- 2022/04/26 06:00 [entrez]
PHST- 2022/04/25 00:00 [pmc-release]
AID - JCLA24457 [pii]
AID - 10.1002/jcla.24457 [doi]
PST - ppublish
SO  - J Clin Lab Anal. 2022 Jun;36(6):e24457. doi: 10.1002/jcla.24457. Epub 2022 Apr 
      25.