Association Analysis of the Polymorphism of Human Leukocyte Antigen-A, -B and -E Gene with Behcet's Disease in Japanese Cohort Using Sequencing-Based Typing Method

Kurata, Riho; Yonezawa, Tomo; Inoko, Hidetoshi

doi:10.15406/moji.2014.01.00013

Cited by 5 publications

(3 citation statements)

References 23 publications

(18 reference statements)

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“…[ 1 9 21 22 ] Furthermore, the major histocompatibility complex (MHC) Class II genes have shown the most convincing genetic correlations with HSP and have been studied in different other autoimmune diseases such as systemic lupus erythematosus, Kawasaki, endometriosis, juvenile idiopathic arthritis (JIA), and Behçet's and Graves' disease (GD). [ 13 23 24 25 26 27 28 29 ]…”

Section: Discussionmentioning

confidence: 99%

HLA-DRB1 gene polymorphisms in Iranian children with Henoch-Schönlein purpura

2018

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Background:People of all ages can suffer from Henoch-Schönlein purpura (HSP), but it is the most common vasculitis in childhood. The most important involving gene is located on chromosome 6p21.3, a region coding for human leukocyte antigens (HLAs). Among HLA genes, because of the high rate of polymorphisms, HLA-DRB1 is estimated to have a strong association with HSP. In this study, we aimed to assess the association of HLA-DRB1 alleles with HSP in Iranian children.Materials and Methods:This study consisted of thirty Iranian children with HSP and 35 healthy controls. Genomic DNA was extracted, and HLA typing was performed by polymerase chain reaction with sequence-specific primers technique.Results:The results have shown that HLA-DRB1*01 and HLA-DRB1*11 (P = 0.002, odds ratio [OR] = 7.579, confidence interval [CI] = 1.934–29.697 and P = 0.039, OR = 3.333, CI = 1.030–10.788), respectively, are the most frequent alleles associated with HSP in Iranian children population. The frequency of other alleles was not significantly different in both groups. The results also show no correlation between HLA types and disease manifestations.Conclusion:According to these results, there is an association between HLA-DRB1*01 and HLA-DRB1*11 gene polymorphisms and susceptibility to HSP in our study group.

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Section: Discussionmentioning

confidence: 99%

HLA-DRB1 gene polymorphisms in Iranian children with Henoch-Schönlein purpura

2018

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“…The association of BD with the HLA-B*51:01 allele in various ethnic groups in Japan and Korea has been frequently observed [ 3 ], while the HLA-A*26:01 allele was detected in BD patients in Greece, Japan and Taiwan [ 32 – 34 ]. Some possible candidate genes for BD have been studied in various HLA-A and-B alleles [ 35 ]. Recently, in Japanese uveitis patients, BD was associated with the HLA-A*26:01 allele at a 37.5% phenotype frequency more than the controls, and so HLA-A*26:01 is a possible marker as a susceptible allele for ophthalmic BD in Japanese ethnics [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics Simulation Reveals the Selective Binding of Human Leukocyte Antigen Alleles Associated with Behçet's Disease

et al. 2015

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Behçet’s disease (BD), a multi-organ inflammatory disorder, is associated with the presence of the human leukocyte antigen (HLA) HLA-B*51 allele in many ethnic groups. The possible antigen involvement of the major histocompatibility complex class I chain related gene A transmembrane (MICA-TM) nonapeptide (AAAAAIFVI) has been reported in BD symptomatic patients. This peptide has also been detected in HLA-A*26:01 positive patients. To investigate the link of BD with these two specific HLA alleles, molecular dynamics (MD) simulations were applied on the MICA-TM nonapeptide binding to the two BD-associated HLA alleles in comparison with the two non-BD-associated HLA alleles (B*35:01 and A*11:01). The MD simulations were applied on the four HLA/MICA-TM peptide complexes in aqueous solution. As a result, stabilization for the incoming MICA-TM was found to be predominantly contributed from van der Waals interactions. The P2/P3 residue close to the N-terminal and the P9 residue at the C-terminal of the MICA-TM nonapeptide served as the anchor for the peptide accommodated at the binding groove of the BD associated HLAs. The MM/PBSA free energy calculation predicted a stronger binding of the HLA/peptide complexes for the BD-associated HLA alleles than for the non-BD-associated ones, with a ranked binding strength of B*51:01 > B*35:01 and A*26:01 > A*11:01. Thus, the HLAs associated with BD pathogenesis expose the binding efficiency with the MICA-TM nonapeptide tighter than the non-associated HLA alleles. In addition, the residues 70, 73, 99, 146, 147 and 159 of the two BD-associated HLAs provided the conserved interaction for the MICA-TM peptide binding.

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“…The association of BD with the HLA-B*51:01 allele in various ethnic groups in Japan and Korea has been frequently observed [29], while the HLA-A*26:01 allele was detected in BD patients in Greece, Japan and Taiwan [52][53][54]. Some possible candidate genes for BD have been studied in various HLA-A and-B alleles [55]. Recently, in Japanese uveitis patients, BD was associated with the HLA-A*26:01 allele at a 37.5% phenotype frequency more than the controls, and so HLA-A*26:01 is a possible marker as a susceptible allele for ophthalmic BD in Japanese ethnics [56].…”

Section: Autoimmune Diseasesmentioning

confidence: 99%

Specific binding of HLAs and antigenic peptides associated with behcet's disease and systemic sclerosis

Kongkaew

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Human leukocyte antigen (HLA) molecules are essential components for immune functions. There play a major role to present antigenic-peptide for T-cell receptor (TCR) recognition and immune activation. Association between HLA genes and infectious as well as autoimmune diseases are identified genetic risk factors. For instance, Beh?et?s disease (BD) and systemic sclerosis (SSc) are autoimmunity result in chronic of multisystemic inflammation and visceral fibrosis, respectively. To investigate the link of HLAs correlated with self-peptides for BD and SSc, molecular dynamics (MD) simulations were applied on the HLAp complexes. For BD, a self-peptide named MICA-TM was modeled for two BD-association such as HLA-A*26:01 and HLA-B*51:01 in comparisons to non-association with BD. SSc simulation were studied on the complexes of topoisomerase 1 (Top1) peptide with various HLA-DR subtypes divided into association (HLA-DRB1*08:02, HLA-DRB1*11:01 and HLA-DRB1*11:04), suspect (HLA-DRB5*01:02) and non-association (HLA-DRB1*01:01) with SSc. The unique interaction for each system was compared to the others in terms of dynamical behaviors and binding free energies. Our results showed that HLAp of diseased suspect and association exhibited high protein stability and increased binding efficiency, in contrast to non-association. Moreover, T-cell receptor bound HLA with self-peptide by minimal criteria of TCR engagement as well as infectious cases. This finding might support mechanism of BD, SSc and autoimmunity TCR-recognition leading to a more understanding and guideline on the treatment for autoimmune diseases.

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Association Analysis of the Polymorphism of Human Leukocyte Antigen-A, -B and -E Gene with Behcet's Disease in Japanese Cohort Using Sequencing-Based Typing Method

Cited by 5 publications

References 23 publications

HLA-DRB1 gene polymorphisms in Iranian children with Henoch-Schönlein purpura

HLA-DRB1 gene polymorphisms in Iranian children with Henoch-Schönlein purpura

Molecular Dynamics Simulation Reveals the Selective Binding of Human Leukocyte Antigen Alleles Associated with Behçet's Disease

Specific binding of HLAs and antigenic peptides associated with behcet's disease and systemic sclerosis

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