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Epistatic Interaction of ERAP1 and HLA-B*51 in Iranian Patients with Behçet’s Disease
Behçet’s Disease (BD) pathogenesis remains unclear, but some genetic loci and environmental factors are proposed to play a role. Here, we investigate the association of the endoplasmic reticulum aminopeptidase-1 (ERAP1) gene variants and HLA-B*51 with BD susceptibility and clinical manifestations in...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279803/ https://www.ncbi.nlm.nih.gov/pubmed/30514861 http://dx.doi.org/10.1038/s41598-018-35700-0 |
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author | Mahmoudi, Mahdi Ashraf-Ganjouei, Amir Javinani, Ali Shahram, Farhad Meguro, Akira Mizuki, Nobuhisa Ahmadzadeh, Nooshin Jafarinejad-Farsangi, Saeideh Mostafaei, Shayan Kavosi, Hoda Faezi, Seyedeh Tahereh Akhlaghi, Maassoumeh Davatchi, Fereydoun |
author_facet | Mahmoudi, Mahdi Ashraf-Ganjouei, Amir Javinani, Ali Shahram, Farhad Meguro, Akira Mizuki, Nobuhisa Ahmadzadeh, Nooshin Jafarinejad-Farsangi, Saeideh Mostafaei, Shayan Kavosi, Hoda Faezi, Seyedeh Tahereh Akhlaghi, Maassoumeh Davatchi, Fereydoun |
author_sort | Mahmoudi, Mahdi |
collection | PubMed |
description | Behçet’s Disease (BD) pathogenesis remains unclear, but some genetic loci and environmental factors are proposed to play a role. Here, we investigate the association of the endoplasmic reticulum aminopeptidase-1 (ERAP1) gene variants and HLA-B*51 with BD susceptibility and clinical manifestations in Iranian patients. In the study, 748 BD patients and 776 healthy individuals were included. The MGB-TaqMan Allelic Discrimination method was used to genotype 10 common missense single nucleotide polymorphisms (SNPs) and one intronic SNP in the ERAP1 gene region. We found no significant association between the 11 SNPs and BD in allelic and genotypic association tests. However, rs30187 showed the strongest association with BD in the recessive genotype model of the risk T allele in HLA-B*51 carriers. Although this became insignificant after correcting for multiple comparisons, the homozygous rs30187 risk allele genotype (TT) increased disease susceptibility in HLA-B*51 carriers in epistasis analysis, and the rs30187 TT recessive genotype showed a significant association with risk of cardiac involvement in the all patients and articular involvements in HLA-B*51 positive patients. Our findings suggest that gene-gene interactions between HLA-B*51 and ERAP1 variants is important for BD development, however, ERAP1 variants which interact with HLA-B*51 may differ among disease phenotypes or populations. |
format | Online Article Text |
id | pubmed-6279803 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62798032018-12-07 Epistatic Interaction of ERAP1 and HLA-B*51 in Iranian Patients with Behçet’s Disease Mahmoudi, Mahdi Ashraf-Ganjouei, Amir Javinani, Ali Shahram, Farhad Meguro, Akira Mizuki, Nobuhisa Ahmadzadeh, Nooshin Jafarinejad-Farsangi, Saeideh Mostafaei, Shayan Kavosi, Hoda Faezi, Seyedeh Tahereh Akhlaghi, Maassoumeh Davatchi, Fereydoun Sci Rep Article Behçet’s Disease (BD) pathogenesis remains unclear, but some genetic loci and environmental factors are proposed to play a role. Here, we investigate the association of the endoplasmic reticulum aminopeptidase-1 (ERAP1) gene variants and HLA-B*51 with BD susceptibility and clinical manifestations in Iranian patients. In the study, 748 BD patients and 776 healthy individuals were included. The MGB-TaqMan Allelic Discrimination method was used to genotype 10 common missense single nucleotide polymorphisms (SNPs) and one intronic SNP in the ERAP1 gene region. We found no significant association between the 11 SNPs and BD in allelic and genotypic association tests. However, rs30187 showed the strongest association with BD in the recessive genotype model of the risk T allele in HLA-B*51 carriers. Although this became insignificant after correcting for multiple comparisons, the homozygous rs30187 risk allele genotype (TT) increased disease susceptibility in HLA-B*51 carriers in epistasis analysis, and the rs30187 TT recessive genotype showed a significant association with risk of cardiac involvement in the all patients and articular involvements in HLA-B*51 positive patients. Our findings suggest that gene-gene interactions between HLA-B*51 and ERAP1 variants is important for BD development, however, ERAP1 variants which interact with HLA-B*51 may differ among disease phenotypes or populations. Nature Publishing Group UK 2018-12-04 /pmc/articles/PMC6279803/ /pubmed/30514861 http://dx.doi.org/10.1038/s41598-018-35700-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Mahmoudi, Mahdi Ashraf-Ganjouei, Amir Javinani, Ali Shahram, Farhad Meguro, Akira Mizuki, Nobuhisa Ahmadzadeh, Nooshin Jafarinejad-Farsangi, Saeideh Mostafaei, Shayan Kavosi, Hoda Faezi, Seyedeh Tahereh Akhlaghi, Maassoumeh Davatchi, Fereydoun Epistatic Interaction of ERAP1 and HLA-B*51 in Iranian Patients with Behçet’s Disease |
title | Epistatic Interaction of ERAP1 and HLA-B*51 in Iranian Patients with Behçet’s Disease |
title_full | Epistatic Interaction of ERAP1 and HLA-B*51 in Iranian Patients with Behçet’s Disease |
title_fullStr | Epistatic Interaction of ERAP1 and HLA-B*51 in Iranian Patients with Behçet’s Disease |
title_full_unstemmed | Epistatic Interaction of ERAP1 and HLA-B*51 in Iranian Patients with Behçet’s Disease |
title_short | Epistatic Interaction of ERAP1 and HLA-B*51 in Iranian Patients with Behçet’s Disease |
title_sort | epistatic interaction of erap1 and hla-b*51 in iranian patients with behçet’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279803/ https://www.ncbi.nlm.nih.gov/pubmed/30514861 http://dx.doi.org/10.1038/s41598-018-35700-0 |
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