PMID- 35751838
OWN - NLM
STAT- MEDLINE
DCOM- 20221028
LR  - 20221207
IS  - 1346-8138 (Electronic)
IS  - 0385-2407 (Linking)
VI  - 49
IP  - 10
DP  - 2022 Oct
TI  - Imputation of the major histocompatibility complex region identifies major 
      independent variants associated with bullous pemphigoid and dermatomyositis in 
      Han Chinese.
PG  - 998-1004
LID - 10.1111/1346-8138.16499 [doi]
AB  - As autoimmune skin diseases, both bullous pemphigoid (BP) and dermatomyositis 
      (DM) show significant associations with the major histocompatibility complex 
      (MHC) region. In fact, the coexistence of BP and DM has been previously reported. 
      Therefore, we hypothesized that there may be a potential genetic correlation 
      between BP and DM. Based on data for 312 BP patients, 128 DM patients, and 6793 
      healthy control subjects, in the MHC region, we imputed single-nucleotide 
      polymorphisms (SNP), insertions and deletions (INDEL), and copy number variations 
      (CNV) using the 1KGP phase 3 dataset and amino acids (AA) and SNP using a Han-MHC 
      reference database. An association study revealed the most significant SNP 
      associated with BP, namely, rs580921 (p = 1.06E-08, odds ratio [OR] = 1.61, 95% 
      confidence interval [CI] = 1.37-1.90), which is located in the C6orf10 gene, and 
      the most significant classic human leukocyte antigen (HLA) allele associated with 
      DM, namely, HLA-DPB1*1701 (p = 6.56E-10, OR = 3.61, 95% CI = 2.40-5.42). Further 
      stepwise regression analyses with rs580921 identified a threonine at position 163 
      of the HLA-B gene as a new independent disease-associated AA, and HLA-DPB1*1701 
      indicated that no loci were significant. Three-dimensional ribbon models revealed 
      that the HLA-B AA position 163 (p = 3.93E-07, OR = 1.64, 95% CI = 1.35-1.98) 
      located in the alpha2 domain of the HLA-B molecule was involved in the process of 
      specific antigen presentation. The calculations showed that there was no 
      significant genetic correlation between BP and DM. Our study identified three 
      significant loci in the MHC region, proving that the HLA region was significantly 
      correlated with BP and DM separately. Our research highlights the key role of the 
      MHC region in disease susceptibility.
CI  - (c) 2022 Japanese Dermatological Association.
FAU - Fan, Wencheng
AU  - Fan W
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Li, Zhuo
AU  - Li Z
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Wang, Yirui
AU  - Wang Y
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Zhang, Chang
AU  - Zhang C
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Liu, Hao
AU  - Liu H
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Wang, Daiyue
AU  - Wang D
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Bai, Yuanming
AU  - Bai Y
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Luo, Sihan
AU  - Luo S
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Li, Yuanyuan
AU  - Li Y
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Qin, Qin
AU  - Qin Q
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Chen, Weiwei
AU  - Chen W
AUID- ORCID: 0000-0002-9581-0502
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Yong, Liang
AU  - Yong L
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Zhen, Qi
AU  - Zhen Q
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Yu, Yafen
AU  - Yu Y
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Ge, Huiyao
AU  - Ge H
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Mao, Yiwen
AU  - Mao Y
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Cao, Lu
AU  - Cao L
AUID- ORCID: 0000-0003-2967-2831
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Zhang, Ruixue
AU  - Zhang R
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Hu, Xia
AU  - Hu X
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Yu, Yanxia
AU  - Yu Y
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
FAU - Li, Bao
AU  - Li B
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - The Comprehensive Lab, College of Basic Medicine, Anhui Medical University, 
      Hefei, China.
FAU - Sun, Liangdan
AU  - Sun L
AUID- ORCID: 0000-0002-8499-5353
AD  - Department of Dermatology, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
AD  - Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, 
      Hefei, China.
AD  - Anhui Province Laboratory of Inflammation and Immune Mediated Diseases, Hefei, 
      China.
AD  - Anhui Provincial Institute of Translational Medicine, Hefei, China.
LA  - eng
GR  - ZHYX2020A005/Anhui Institute of Translational Medicine/
GR  - 2021lcxk008/Clinical medicine discipline construction project of Anhui Medical 
      University/
GR  - GXXT-2020-064/The University Synergy Innovation Program of Anhui Province/
PT  - Journal Article
DEP - 20220625
PL  - England
TA  - J Dermatol
JT  - The Journal of dermatology
JID - 7600545
RN  - 0 (Amino Acids)
RN  - 0 (HLA-B Antigens)
RN  - 2ZD004190S (Threonine)
SB  - IM
MH  - Humans
MH  - Alleles
MH  - Amino Acids/genetics
MH  - Asian People/genetics
MH  - China/epidemiology
MH  - *Dermatomyositis/genetics
MH  - DNA Copy Number Variations
MH  - Genetic Predisposition to Disease
MH  - HLA-B Antigens/genetics
MH  - Major Histocompatibility Complex/genetics
MH  - *Pemphigoid, Bullous/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Threonine/genetics
OTO - NOTNLM
OT  - bullous pemphigoid
OT  - dermatomyositis
OT  - imputation
OT  - major histocompatibility complex
OT  - stepwise regression analysis
EDAT- 2022/06/26 06:00
MHDA- 2022/10/12 06:00
CRDT- 2022/06/25 11:23
PHST- 2022/04/29 00:00 [revised]
PHST- 2022/01/08 00:00 [received]
PHST- 2022/06/05 00:00 [accepted]
PHST- 2022/06/26 06:00 [pubmed]
PHST- 2022/10/12 06:00 [medline]
PHST- 2022/06/25 11:23 [entrez]
AID - 10.1111/1346-8138.16499 [doi]
PST - ppublish
SO  - J Dermatol. 2022 Oct;49(10):998-1004. doi: 10.1111/1346-8138.16499. Epub 2022 Jun 
      25.