HLA-DRB1 allele association with rheumatoid arthritis susceptibility and severity in Syria

Abstract

IntroductionRheumatoid arthritis (RA) is a complex multifactorial chronic disease. The importance of human leukocyte antigen as a major genetic risk factor for RA was studied worldwide. Although it is widely distributed in different Syrian areas, studies of human leukocyte antigen (HLA) alleles’ role are absent. ObjectiveThe aim of our study was to determine the association of HLA-DRB1 alleles with the susceptibility and severity of RA in Syria. Patients and methodsEightysix RA patients and 200 healthy controls from Syria were genotyped using polymerase chain reaction with sequencespecific primer (PCR-SSP). Anti-CCP antibodies were measured by ELISA. Rheumatoid factor (RF), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and disease activity score 28 (DAS-28) values were obtained from patients’ medical records. DAS-28 was used to assess the clinical severity of the patients. ResultsThe HLA-DRB1*01, *04, and *10 frequencies showed a strong association with the disease susceptibility (OR=2.29, 95% CI=1.11–4.75, P=0.022; OR=3.16, 95% CI=2.08–4.8, P<0.0001; OR=2.43, 95% CI=1.07–5.51, P=0.029 respectively), while the frequencies of HLA-DRB1*11, and *13 were significantly lower in RA patients than in controls (OR=0.49, 95% CI=0.3–0.8, P=0.004; OR=0.32, 95% CI=0.15–0.69, P=0.002, respectively). The other HLA-DRB1 alleles showed no significant difference. The frequency of anti-CCP antibodies was higher in shared epitope (SE) positive patients compared with SE-negative patients (OR=5.5, 95% CI=2–15.1, P=0.00054). DAS-28 of RA patients didn’t show significant difference between the SE negative and the SE positive groups. ConclusionOur results indicate that HLA-DRB1*01, *04, and *10 alleles are related with RA, while HLA-DRB1*11 and *13 protect against RA in the Syrian population.