ERAP1, ERAP2, and Two Copies of HLA-Aw19 Alleles Increase the Risk for Birdshot Chorioretinopathy in HLA-A29 Carriers
| Autor: | Xiaodong Bai, Dominique Monnet, Thierry Tabary, Carmelo Romano, Jack A. Kosmicki, Sahar Gelfman, Antoine P. Brézin, Eli A. Stahl, Manuel A. R. Ferreira, Jonathan Weyne, Aris Baras, Giovanni Coppola, Arden Moscati, Jacques H. M. Cohen, Blerta Cooper, Sarah Wolf, Ann J. Ligocki, Jan Freudenberg, John D. Overton |
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| Rok vydání: | 2021 |
| Předmět: |
Heterozygote
Genotyping Techniques HLA-A33 Human leukocyte antigen Biology ERAP1 Aminopeptidases Polymorphism Single Nucleotide ERAP2 Minor Histocompatibility Antigens Gene Frequency Risk Factors Genotype medicine Odds Ratio Genetics Humans Genetic Predisposition to Disease Allele Allele frequency Alleles HLA-A Antigens Haplotype Birdshot Chorioretinopathy Odds ratio medicine.disease Birdshot chorioretinopathy birdshot Haplotypes HLA-Aw19 Cohort Immunology Expression quantitative trait loci Multiplex Polymerase Chain Reaction Genome-Wide Association Study |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 |
| Popis: | PurposeBirdshot Chorioretinopathy (BSCR) is strongly associated with HLA-A29. This study was designed to elucidate the genetic modifiers of BSCR in HLA-A29 carriers.MethodsWe sequenced the largest BSCR cohort to date, including 286 cases and 108 HLA-A29 positive controls to perform genome wide common and rare variant associations. We further typed the HLA alleles of cases and 45,386 HLA-A29 controls of European ancestry to identify HLA alleles that associate with BSCR risk.ResultsCarrying a second allele that belongs to the HLA-Aw19 broad antigen family (including HLA-A29, A30, A31, and A33) increases the risk for BSCR (OR=4.44, p=2.2e-03). This result was validated by comparing allele frequencies to large HLA-A29-controlled cohorts (n=45,386, OR>2.5, pConclusionsThe genetic factors increasing BSCR risk demonstrate a pattern of increased processing, as well as increased presentation of ERAP2 specific peptides. This suggests a mechanism in which exceeding a peptide presentation threshold activates the immune response in choroids of A29 carriers. |
| Databáze: | OpenAIRE |
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