Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behçet’s disease susceptibility
| Autor: | Elaine F. Remmers, Ahmet Gül, Yohei Kirino, Sofia A. Oliveira, Fahmida Ghaderibarmi, Bahar Sadeghi Abdollahi, Daniel L. Kastner, Mary Blake, Masaki Takeuchi, Michael J. Ombrello, Nobuhisa Mizuki, Yilmaz Ozyazgan, Massimo Gadina, Fereydoun Davatchi, Atsuhisa Ueda, Burak Erer, Julie Le, Vânia Francisco, Ilknur Tugal-Tutkun, Abdolhadi Nadji, Niloofar Mojarad Shafiee, Akira Meguro, Colleen Satorius, Farhad Shahram, Tatsukata Kawagoe, Yoshiaki Ishigatsubo, Emire Seyahi, Shigeaki Ohno, Duran Ustek, Inês Sousa |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male Genotype Turkey Single-nucleotide polymorphism Disease Behcet's disease Biology Iran Polymorphism Single Nucleotide Article 03 medical and health sciences 0302 clinical medicine Genetics medicine SNP Humans Genetic Predisposition to Disease Allele Genotyping Alleles 030203 arthritis & rheumatology Behcet Syndrome Tag SNP medicine.disease 3. Good health 030104 developmental biology Genetic Loci Case-Control Studies Immunology Female Genome-Wide Association Study |
| Zdroj: | Nature genetics |
| ISSN: | 1546-1718 1061-4036 |
| Popis: | Daniel Kastner, Elaine Remmers and colleagues perform an association study of Behcet's disease based on dense genotyping of immune-related loci. They identify new association signals near genes involved in host response to microbial exposure and extend evidence for shared susceptibility loci with Crohn's disease and leprosy. We analyzed 1,900 Turkish Behcet's disease cases and 1,779 controls genotyped with the Immunochip. The most significantly associated SNP was rs1050502, a tag SNP for HLA-B*51. In the Turkish discovery set, we identified three new risk loci, IL1A–IL1B, IRF8, and CEBPB–PTPN1, with genome-wide significance (P < 5 × 10−8) by direct genotyping and ADO–EGR2 by imputation. We replicated the ADO–EGR2, IRF8, and CEBPB–PTPN1 loci by genotyping 969 Iranian cases and 826 controls. Imputed data in 608 Japanese cases and 737 controls further replicated ADO–EGR2 and IRF8, and meta-analysis additionally identified RIPK2 and LACC1. The disease-associated allele of rs4402765, the lead marker at IL1A–IL1B, was associated with both decreased IL-1α and increased IL-1β production. ABO non-secretor genotypes for two ancestry-specific FUT2 SNPs showed strong disease association (P = 5.89 × 10−15). Our findings extend the list of susceptibility genes shared with Crohn's disease and leprosy and implicate mucosal factors and the innate immune response to microbial exposure in Behcet's disease susceptibility. |
| Databáze: | OpenAIRE |
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