HLA-DRB1 allele distribution in Chilean population: insights into rheumatoid arthritis susceptibility and protection

IntroductionRheumatoid arthritis (RA) is an autoimmune disease influenced by genetic factors, particularly HLA-DRB1 alleles. The objective of this study was to characterize the distribution of HLA-DRB1 alleles in Chilean RA patients and healthy controls (HC) and evaluate associations with susceptibi...

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Main Authors: Diego Catalán, Lilian Soto, Óscar Neira, María C. Cuéllar-Gutiérrez, Roberto Díaz-Peña, Octavio Aravena, Eduard Palou, Montserrat Carrascal, Juan C. Aguillón, Jaxaira Maggi
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Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1594723/full
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author Diego Catalán
Lilian Soto
Lilian Soto
Óscar Neira
María C. Cuéllar-Gutiérrez
Roberto Díaz-Peña
Roberto Díaz-Peña
Octavio Aravena
Eduard Palou
Montserrat Carrascal
Juan C. Aguillón
Jaxaira Maggi
author_facet Diego Catalán
Lilian Soto
Lilian Soto
Óscar Neira
María C. Cuéllar-Gutiérrez
Roberto Díaz-Peña
Roberto Díaz-Peña
Octavio Aravena
Eduard Palou
Montserrat Carrascal
Juan C. Aguillón
Jaxaira Maggi
author_sort Diego Catalán
collection DOAJ
description IntroductionRheumatoid arthritis (RA) is an autoimmune disease influenced by genetic factors, particularly HLA-DRB1 alleles. The objective of this study was to characterize the distribution of HLA-DRB1 alleles in Chilean RA patients and healthy controls (HC) and evaluate associations with susceptibility or protection, autoantibody seropositivity, and disease activity.MethodsWe genotyped 367 RA patients and 623 HC for HLA-DRB1 using PCR-SSO. Then, we examined allele frequencies and distribution, including known RA risk alleles of the “Shared Epitope” (SE) of HLA-DRB1 and protective (PR) alleles, using the Chi-square or Fisher’s exact tests. Odds ratios with 95% confidence intervals were calculated to measure the degree of association, and unpaired T-tests were used to compare continuous variables.ResultsThe most frequent SE alleles among RA patients were *04:01 (16.1%), *04:04 (13.9%), and *14:02 (11.7%). SE alleles *04:01, *04:04, *04:05, *04:08, and *10:01, along with non-SE alleles *09:01 and *15:02, were associated with RA susceptibility. In addition, allele *14:02 showed an association with the presence of anti-cyclic citrullinated peptides (anti-CCP) antibodies. Meanwhile, PR alleles *11:01 (14.8%) and *16:02 (9.8%) were observed most frequently in HC and RA patients, respectively. PR alleles *11:01, *11:04, and *13:01, as well as the non-PR alleles *15:01, *04:07, *03:01, *07:01, and *08:02, were associated with protection from RA, and showed no significant associations with autoantibody seropositivity.DiscussionThis study provides a comprehensive overview of HLA-DRB1 allele distribution in the Chilean population, identifying both well-known and novel allele associations with RA susceptibility, protection, and disease activity.
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spelling doaj-art-09a116032f4d40e493e011ed6fcaa06a2025-08-20T02:15:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15947231594723HLA-DRB1 allele distribution in Chilean population: insights into rheumatoid arthritis susceptibility and protectionDiego Catalán0Lilian Soto1Lilian Soto2Óscar Neira3María C. Cuéllar-Gutiérrez4Roberto Díaz-Peña5Roberto Díaz-Peña6Octavio Aravena7Eduard Palou8Montserrat Carrascal9Juan C. Aguillón10Jaxaira Maggi11Immune Regulation and Tolerance Research Group (IRT Group), Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileImmune Regulation and Tolerance Research Group (IRT Group), Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileSección Reumatología, Departamento de Medicina Interna, Hospital Clínico de la Universidad de Chile, Santiago, ChileHospital del Salvador, Universidad de Chile, Santiago, ChileHospital del Salvador, Universidad de Chile, Santiago, ChileFacultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, ChileImmunogenetics Lab, Fundación Pública Galega de Medicina Xenómica, Servizo Galego de Saúde (SERGAS), Grupo de MedicinaXenómica-Universidade de Santiago de Compostela (USC), Instituto de investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, SpainImmune Regulation and Tolerance Research Group (IRT Group), Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileServicio de Inmunología, Hospital Clínic de Barcelona, Barcelona, SpainBiological and Environmental Proteomics Group, Institute of Biomedical Research of Barcelona, Spanish National Research Council (IIBB-CSIC/IDIBAPS), Barcelona, SpainImmune Regulation and Tolerance Research Group (IRT Group), Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileBiological and Environmental Proteomics Group, Institute of Biomedical Research of Barcelona, Spanish National Research Council (IIBB-CSIC/IDIBAPS), Barcelona, SpainIntroductionRheumatoid arthritis (RA) is an autoimmune disease influenced by genetic factors, particularly HLA-DRB1 alleles. The objective of this study was to characterize the distribution of HLA-DRB1 alleles in Chilean RA patients and healthy controls (HC) and evaluate associations with susceptibility or protection, autoantibody seropositivity, and disease activity.MethodsWe genotyped 367 RA patients and 623 HC for HLA-DRB1 using PCR-SSO. Then, we examined allele frequencies and distribution, including known RA risk alleles of the “Shared Epitope” (SE) of HLA-DRB1 and protective (PR) alleles, using the Chi-square or Fisher’s exact tests. Odds ratios with 95% confidence intervals were calculated to measure the degree of association, and unpaired T-tests were used to compare continuous variables.ResultsThe most frequent SE alleles among RA patients were *04:01 (16.1%), *04:04 (13.9%), and *14:02 (11.7%). SE alleles *04:01, *04:04, *04:05, *04:08, and *10:01, along with non-SE alleles *09:01 and *15:02, were associated with RA susceptibility. In addition, allele *14:02 showed an association with the presence of anti-cyclic citrullinated peptides (anti-CCP) antibodies. Meanwhile, PR alleles *11:01 (14.8%) and *16:02 (9.8%) were observed most frequently in HC and RA patients, respectively. PR alleles *11:01, *11:04, and *13:01, as well as the non-PR alleles *15:01, *04:07, *03:01, *07:01, and *08:02, were associated with protection from RA, and showed no significant associations with autoantibody seropositivity.DiscussionThis study provides a comprehensive overview of HLA-DRB1 allele distribution in the Chilean population, identifying both well-known and novel allele associations with RA susceptibility, protection, and disease activity.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1594723/fullrheumatoid arthritisHLA-DRB1 allelesshared epitopeanti-CCP antibodiesChilean cohort
spellingShingle Diego Catalán
Lilian Soto
Lilian Soto
Óscar Neira
María C. Cuéllar-Gutiérrez
Roberto Díaz-Peña
Roberto Díaz-Peña
Octavio Aravena
Eduard Palou
Montserrat Carrascal
Juan C. Aguillón
Jaxaira Maggi
HLA-DRB1 allele distribution in Chilean population: insights into rheumatoid arthritis susceptibility and protection
Frontiers in Immunology
rheumatoid arthritis
HLA-DRB1 alleles
shared epitope
anti-CCP antibodies
Chilean cohort
title HLA-DRB1 allele distribution in Chilean population: insights into rheumatoid arthritis susceptibility and protection
title_full HLA-DRB1 allele distribution in Chilean population: insights into rheumatoid arthritis susceptibility and protection
title_fullStr HLA-DRB1 allele distribution in Chilean population: insights into rheumatoid arthritis susceptibility and protection
title_full_unstemmed HLA-DRB1 allele distribution in Chilean population: insights into rheumatoid arthritis susceptibility and protection
title_short HLA-DRB1 allele distribution in Chilean population: insights into rheumatoid arthritis susceptibility and protection
title_sort hla drb1 allele distribution in chilean population insights into rheumatoid arthritis susceptibility and protection
topic rheumatoid arthritis
HLA-DRB1 alleles
shared epitope
anti-CCP antibodies
Chilean cohort
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1594723/full
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