Abstract
Because of genetic complex and variations of auto antibodies of rheumatoid arthritis (RA) in different populations, the data on the association of HLA-DRB1 alleles in anti-citrullinated protein antibody of (ACPA) RA were inconsistent. The purpose of the study is to systematically summarize results of published data through performing a meta-analysis using data in which HLA-DRB1 alleles are associated with ACPApositive RA and ACPA-negative RA. In this study, we collected data from 12 studies with 13,861 cases and 12,896 controls. Information in these studies included HLADRB1 typing and ACPA status from different countries. Odds ratios (ORs) and corresponding 95% confidence intervals (CI) were used to analyze the association of different HLA-DRB1 alleles with ACPA-positive RA or ACPA-negative RA. To correct skewing data, the analysis of ACPA-status was stratified by patient distribution. Our analyses indicate that in ACPA-positive RA, all patients with RA had significantly higher frequencies of HLA-DRB1*01, *04, *0401, *0405, *07, *11, *13 and *14 than controls. One of the HLA-DRB1*07, *11, *13 and *14 showed protective association with RA. In addition, HLA-DRB1*03, *10 and *12 had more influence than control to RA in European populations; the HLA-DRB1*03 and *12 alleles were associated with the protection. In ACPA-negative RA, only DRB1*07 was associated with the protection (OR 0.53 [95% CI 0.36 - 0.76]) among all HLA-DRB1 alleles in European populations. In ACPA-positive RA, currently available results indicate that *01, *04, *0401 and *0405 are susceptible, while HLA-DRB1*07, *11, *13 and *14 are protective in all populations. While the HLA-DRB1*10 is susceptible, HLA-DRB1*03 and *12 show protective association with RA in European populations. Additionally, regardless of the positive or negative ACPA, the DRB1*07 is always associated with protection in European populations.
Highlights
Rheumatoid arthritis (RA) is an autoimmune and worldwide prevalent disease that is characterized by the symmetric joint destruction and disability [1]
12 articles [5] [11] [18]-[27] were selected and analyzed. These studies include a total of 13,861 cases and 12,896 controls in the analysis of the association of Human Leukocyte Antigen (HLA)-DRB1 alleles with anti-citrullinated protein antibody of (ACPA)-positive rheumatoid arthritis (RA) and ACPA-negative RA in European, Asia and African patients
Our present study shows that the HLA-DRB1*01, *04, *0401, *0405 play predisposing roles in the correlation with ACPA-positive RA whereas the HLA-DRB1*11, *13 and *14 are associated with ACPA-positive protection regardless of European populations or Asia or/and African populations
Summary
Rheumatoid arthritis (RA) is an autoimmune and worldwide prevalent disease that is characterized by the symmetric joint destruction and disability [1]. The prevalence of RA in the patients living in variety of areas is presumably associated with the complex interaction between specific environmental conditions of geographical areas and the polymorphism of the immune response genes in the population [2]. Based on the fact that the shared epitope (SE) is located in positions of 70 - 74 (QKRAA, RRRAA, or QRRAA) of the HLA-DRB1 chain, the hypothesis that the SE HLA-DRB1 alleles were associated with developing RA was generated [5] [6]. The hypothesis provides the theoretical basis of further investigating the effects of the HLA alleles to the RA [7] [8]. Because of the complexity of the HLA region, not all HLA SE alleles carried susceptibility for RA [9]
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