HLA-DRB1*07:01 and *08:02 Alleles Confer a Protective Effect Against ACPA-Positive Rheumatoid Arthritis in a Latin American Admixed Population

SIMPLE SUMMARY: The focus of the genetic studies on rheumatoid arthritis has been on Europeans or European-derived populations, with limited information available on other populations, especially in Latin America. The aim of the present study was to test previously reported HLA markers, the most important genetic contributors for the risk of developing rheumatoid arthritis, associated with anti-citrullinated protein antibodies-positive rheumatoid arthritis in a Latin American population with admixed ancestry. Our study shows for the first time an association between HLA-DRB1*07:01 and *08:02 alleles and protection against anti-citrullinated protein antibodies-positive rheumatoid arthritis in the Chilean population. In addition, our results seem to support the existence of differentiated genomic patterns in Chilean, and probably other Latin American populations, that are not the same that the found in Europeans regarding to loci repeatedly involved in rheumatoid arthritis. Identifying relationships between HLA-DRB1 alleles and rheumatoid arthritis is important for identifying disease associations in different ethnic groups in order to reach a better understanding of rheumatoid arthritis worldwide. ABSTRACT: HLA-DRB1 shared epitope (SE) alleles are important genetic contributors for the risk of developing anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis (RA), particularly in Caucasians. We aimed to analyze the contribution of HLA-DRB1 alleles and single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC) region to the susceptibility to develop ACPA-positive RA in a Latin American (LA) population with admixed ancestry. A total of 289 ACPA-positive RA patients and 510 controls were enrolled in this study. The presence of HLA-DRB1*04:01, *09:01 and *10:01 was increased in ACPA-positive RA patients compared with healthy controls (p < 0.0001, p < 0.001 and p < 0.01, respectively), whereas DRB1*07:01 and *08:02 was associated with a decreased risk of ACPA-positive RA (p < 0.001 and p < 0.01, respectively). These results showed a strong correlation with estimates from studies in Asians but not in Caucasian populations. The present study describes the protective effects of the HLA-DRB1*07:01 and *08:02 alleles in ACPA-positive RA patients in a LA population for the first time. Identifying relationships between HLA-DRB1 alleles and RA is important for identifying disease associations in different ethnic groups in order to reach a better understanding of RA worldwide.