Journal ArticleDOI
Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behçet's disease
Yun Jong Lee,Yukihiro Horie,Graham R. Wallace,Yong Seok Choi,Ji Ah Park,Ji Yong Choi,Ran Song,Young Mo Kang,Seong Wook Kang,Han Joo Baek,Nobuyoshi Kitaichi,Akira Meguro,Nobuhisa Mizuki,Kenichi Namba,Susumu Ishida,Jinhyun Kim,Edyta Niemczyk,Eun Young Lee,Yeong Wook Song,Shigeaki Ohno,Eun Bong Lee +20 more
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TLDR
A genome-wide association study using DNA samples from a Korean population and a replication study in a Japanese population suggest that a GIMAP cluster is a novel susceptibility locus for BD, which is involved in T-cell survival, and T- cell aberration can contribute to the development of BD.Abstract:
Objectives To identify non-major histocompatibility complex susceptible genes that might contribute to Behcet9s disease (BD). Methods We performed a genome-wide association study using DNA samples from a Korean population consisting of 379 BD patients and 800 controls. A replication study was performed in a Japanese population (363 BD patients and 272 controls). To evaluate the functional implication of the target single nucleotide polymorphisms (SNP), gene expression levels in peripheral T cells, allele-specific modulation of promoter activity and biological effect of mRNA knockdown were investigated. Results We found a novel association of BD to the GIMAP locus, mapped to chromosome 7q36.1 (rs1608157, p=6.01×10 −8 in a minor allele dominant model; rs11769828, allele based p=1.60×10 −6 ). A fine mapping study identified an association with four additional SNP: rs1522596 (OR=1.45, p=7.70×10 −6 ) in GIMAP4 ; rs10266069 (OR=1.32, p=2.67×10 −4 ) and rs10256482 (OR=1.27, p=5.27×10 −4 ) in GIMAP2 ; and rs2286900 (OR=1.61, p=3.53×10 −5 ) in GIMAP1 areas. Replication study using DNA samples from the Japanese population validated the significant association between BD and the GIMAP locus. The GIMAP4 promoter construct plasmid with the minor allele of rs1608157 displayed significantly lower activity than one with the major allele. Moreover, CD4 T cells from BD patients showed a lower level of GIMAP4 mRNA, and GIMAP4 knockdown was protective against Fas-mediated apoptosis. Conclusions These results suggest that a GIMAP cluster is a novel susceptibility locus for BD, which is involved in T-cell survival, and T-cell aberration can contribute to the development of BD.read more
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Journal ArticleDOI
Behçet's disease: A comprehensive review with a focus on epidemiology, etiology and clinical features, and management of mucocutaneous lesions
TL;DR: Male sex, younger age of onset and increased number of organs involved at the diagnosis are associated with a more severe disease and, therefore, require more aggressive treatment.
Journal ArticleDOI
Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia
Mark J. Kiel,Thirunavukkarasu Velusamy,Delphine Rolland,Anagh A. Sahasrabuddhe,Fuzon Chung,Nathanael G. Bailey,Alexandra Schrader,Bo Li,Jun Li,Ayse Bilge Ozel,Bryan L. Betz,Roberto N. Miranda,L. Jeffrey Medeiros,Lili Zhao,Marco Herling,Megan S. Lim,Kojo S.J. Elenitoba-Johnson +16 more
TL;DR: A portrait of the mutational landscape of T-PLL is provided and implicate deregulation of DNA repair and epigenetic modulators as well as high-frequency mutational activation of the IL2RG-JAK1- JAK3-STAT5B axis in the pathogenesis of T.PLL.
Journal ArticleDOI
The immunogenetics of Behçet's disease: A comprehensive review.
TL;DR: target next-generation sequencing has revealed the involvement of rare nonsynonymous variants of IL23R, TLR4, NOD2, and MEFV in Behçet's disease pathogenesis, and epistasis observed between HLA-B*51 and the risk coding haplotype of the endoplasmic reticulum-associated protease, ERAP1 provides a clue that an HLA class I-peptide presentation-based mechanism contributes to this complex disease.
Journal ArticleDOI
Behçet's Disease: An Overview of Etiopathogenesis
Pietro Leccese,Erkan Alpsoy +1 more
TL;DR: An overview of the most recent advances on Behçet's disease etiopathogenesis is provided, finding association with HLA-B*51 and increased IL-17 response seems to have an important role in neutrophil activity.
Journal ArticleDOI
Update on the therapy of Behçet disease.
Zeinab Saleh,Thurayya Arayssi +1 more
TL;DR: Treatment of Behçet disease continues to be based largely on anecdotal case reports, case series, and a few randomized clinical trials.
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Journal Article
Criteria for diagnosis of Behçet's disease
Journal ArticleDOI
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Journal ArticleDOI
Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease
Elaine F. Remmers,Fulya Cosan,Yohei Kirino,Michael J. Ombrello,Neslihan Abaci,Colleen Satorius,Julie M. Le,Barbara Yang,Benjamin D. Korman,Aris Cakiris,Oznur Aglar,Zeliha Emrence,Hulya Azakli,Duran Ustek,Ilknur Tugal-Tutkun,Gulsen Akman-Demir,Wei-Wei Chen,Christopher I. Amos,Michael B. Dizon,Afet Akdag Kose,Gülsevim Azizlerli,Burak Erer,Oliver J. Brand,Virginia G. Kaklamani,Phaedon G. Kaklamanis,Eldad Ben-Chetrit,Miles Stanford,Farida Fortune,Marwen Ghabra,William E R Ollier,Young-Hun Cho,Dongsik Bang,John M O'Shea,Graham R. Wallace,Massimo Gadina,Daniel L. Kastner,Ahmet Gül +36 more
TL;DR: The known association of Behçet's disease with HLA-B*51 was confirmed and a second, independent association within the MHC Class I region was identified and the disease-associated IL10 variant was associated with diminished mRNA expression and low protein production.
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