PMID- 33911813
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220422
IS  - 2005-3894 (Electronic)
IS  - 1013-9087 (Print)
IS  - 1013-9087 (Linking)
VI  - 33
IP  - 1
DP  - 2021 Feb
TI  - A Large-Scale, Stratified Genetic Analysis of the Major Histocompatibility 
      Complex Region in Early- and Late-Onset Psoriasis in China.
PG  - 61-67
LID - 10.5021/ad.2021.33.1.61 [doi]
AB  - BACKGROUND: Psoriasis vulgaris is a chronic inflammatory skin disease which occur 
      at any age. It can be clinically classified into two age-onset subtypes: 
      early-onset psoriasis (EOP; <40 years) and late-onset psoriasis (LOP; >/=40 years). 
      More evidence showed EOP and LOP have different genetic architecture, notably the 
      risk allele human leukocyte antigen (HLA)-C(*)06:02 located within the major 
      histocompatibility complex (MHC) region, which was reported to be the outstanding 
      variant associated with EOP. However, genetic structure of EOP and LOP have not 
      been fully elucidated. OBJECTIVE: To investigated HLA genetic heterogeneity 
      between EOP and LOP in China. METHODS: We first calculated the MHC-based 
      heritability of EOP and LOP respectively. Then, we conducted a large-scale, 
      stratified analysis including 7,097 EOP, 1,337 LOP patients, and 9,906 healthy 
      controls by using MHC target sequencing data from a previous study. RESULTS: We 
      observed that HLA alleles collectively explained a larger heritability of EOP 
      (27.4%) than LOP (11.3%). Further association analysis identified three 
      independent loci (HLA-C(*)01:02, p=6.70x10(-8); HLA-A amino acid position 9, 
      p=3.27x10(-17); and HLA-A amino acid position 161, p=5.75x10(-10)) that confer 
      specific susceptibility to EOP. Our data also confirmed HLA-C(*)06:02 as an 
      independent psoriasis-associated variant, contributing a higher degree of risk to 
      EOP than LOP. Moreover, case-case analysis confirmed that HLA-C(*)06:02-positive 
      psoriasis patients have earlier onset. CONCLUSION: Our analysis indicating that 
      different genetic background underlie the EOP and LOP. We believe these findings 
      will serve to predict psoriasis risk in the future and facilitate clinical 
      decision.
CI  - Copyright (c) 2021 The Korean Dermatological Association and The Korean Society for 
      Investigative Dermatology.
FAU - Zhou, Yi
AU  - Zhou Y
AUID- ORCID: 0000-0002-7887-6120
AD  - Department of Dermatology and Institute of Dermatology, First Affiliated 
      Hospital, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, 
      Hefei, China.
FAU - Cai, Minglong
AU  - Cai M
AUID- ORCID: 0000-0002-5038-3703
AD  - Department of Dermatology and Institute of Dermatology, First Affiliated 
      Hospital, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, 
      Hefei, China.
FAU - Sheng, Yujun
AU  - Sheng Y
AUID- ORCID: 0000-0002-6022-3359
AD  - Department of Dermatology and Institute of Dermatology, First Affiliated 
      Hospital, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, 
      Hefei, China.
FAU - Zhang, Xuejun
AU  - Zhang X
AUID- ORCID: 0000-0001-6881-9504
AD  - Department of Dermatology and Institute of Dermatology, First Affiliated 
      Hospital, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, 
      Hefei, China.
LA  - eng
PT  - Journal Article
DEP - 20201230
PL  - Korea (South)
TA  - Ann Dermatol
JT  - Annals of dermatology
JID - 8916577
PMC - PMC7875217
OTO - NOTNLM
OT  - Genetic heterogeneity
OT  - Genetic susceptibility
OT  - Genotype-phenotype association
OT  - Major histocompatibility complex
OT  - Psoriasis
COIS- CONFLICTS OF INTEREST: The authors have nothing to disclose.
EDAT- 2021/04/30 06:00
MHDA- 2021/04/30 06:01
PMCR- 2021/02/01
CRDT- 2021/04/29 06:22
PHST- 2020/04/08 00:00 [received]
PHST- 2020/08/11 00:00 [revised]
PHST- 2020/08/18 00:00 [accepted]
PHST- 2021/04/29 06:22 [entrez]
PHST- 2021/04/30 06:00 [pubmed]
PHST- 2021/04/30 06:01 [medline]
PHST- 2021/02/01 00:00 [pmc-release]
AID - 10.5021/ad.2021.33.1.61 [doi]
PST - ppublish
SO  - Ann Dermatol. 2021 Feb;33(1):61-67. doi: 10.5021/ad.2021.33.1.61. Epub 2020 Dec 
      30.