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A Comprehensive Overview on the Genetics of Behcet's Disease Publisher Pubmed



Mahmoudi M1, 4 ; Aslani S1 ; Meguro A2 ; Akhtari M1, 4 ; Fatahi Y3, 5 ; Mizuki N2 ; Shahram F1
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  3. 3. Faculty of Pharmacy, Department of Pharmaceutical Nanotechnology, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: International Reviews of Immunology Published:2022


Abstract

Behcet's disease (BD) is a systemic and inflammatory disease, characterized mainly by recurrent oral and genital ulcers, eye involvement, and skin lesions. Although the exact etiopathogenesis of BD remains unrevealed, a bulk of studies have implicated the genetic contributing factors as critical players in disease predisposition. In countries along the Silk Road, human leukocyte antigen (HLA)-B51 has been reported as the strongest genetically associated factor for BD. Genome-wide association studies, local genetic polymorphism studies, and meta-analysis of combined data from Turkish, Iranian, and Japanese populations have also identified new genetic associations with BD. Among these, other HLA alleles such as HLA-B*15, HLA-B*27, HLA-B*57, and HLA-A*26 have been found as independent risk factors for BD, whereas HLA-B*49 and HLA-A*03 are independent protective alleles for BD. Moreover, other genes have also reached the genome-wide significance level of association with BD susceptibility, including IL10, IL23R-IL12RB2, IL12A, CCR1-CCR3, STAT4, TNFAIP3, ERAP1, KLRC4, and FUT2. Also, several rare nonsynonymous variants in TLR4, IL23R, NOD2, and MEFV genes have been reported to be involved in BD pathogenesis. According to genetic determinants in the loci outside the MHC region that are contributed to the host defense, immunity, and inflammation pathways, it is suggested that immune responses to the pathogen as an important environmental factor and mucosal immunity contribute to BD susceptibility. © 2020 Taylor & Francis Group, LLC.
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