Worldwide population studies have generally agreed that rheumatoid arthritis (RA) is associated with a group of HLA-DRB1 alleles which share a common amino acid sequence at residues 70-74. This represents the first study to investigate the association of HLA-DRB1 genes with susceptibility to RA amongst Malay, Chinese and Indian ethnic groups in Malaysia. One hundred and thirty three RA patients and one hundred and sixty seven healthy controls were recruited. The HLA-DRB1 alleles were studied using the Phototyping method. The subtypes of HLA-DR4 were detected by "high resolution" PCR-SSP DRB1*04 typing techniques. The prevalence of HLA-DRB1*0405 was significantly higher in Malay patients with RA than in healthy controls (28.9 vs. 8.3%, p = 0.0016, OR = 4.48, 95% CI = 1.26-16.69). Similarly, DRB1*0405 was more common in Chinese RA patients than in controls (30.0 vs. 6.7%, p = 0.0029, OR = 6.00, 95% CI = 1.67-23.48). In addition, DRB1*0901 was a predisposing factor (32.0 vs. 6.7%,p = 0.0015, OR = 6.59, 95% CI = 1.85-25.64) and *0301/04 had a protective role (4.0vs. 25.0%, p = 0.00562, OR = 0.13, 95% CI = 0.02-0.62) in Malaysian Chinese RA. RA in Indians was associated with DRB1*1001 (51.1 vs. 8.5%,p = 0.00002, OR = 11.24, 95% CI = 3.13-44.18). DRB1*0701 (13.3 vs. 42.6%,p = 0.0022, OR = 2.73, 95% CI = 1.40-5.37) may have a protective effect. Therefore, in the Malaysian population, RA is primarily associated with the QRRAA motif, and we suggest that genetic factors play a crucial role in the pathogenesis of RA, compared to environmental factors.
OBJECTIVE:
To assess the relationship between the HLA-DRB1 genes with disease severity as assessed by radiological erosions in Malaysian patients with rheumatoid arthritis (RA).
METHODS:
In this cross-sectional study, we studied 61 RA patients who fulfilled the ACR criteria for the diagnosis of RA. HLA-DRB1 genotyping was performed by sequence specific primer (SSP) - PCR. Radiological grading and erosive score of the hands and wrists was calculated according to the Larsen-Dale method. Demographic data and treatment given to the patients were obtained from their case records.
RESULTS:
Fifty-six females and five males were studied from three ethnic groups. In 57 patients with erosions, rheumatoid factor was detected in 80%, HLA-DR4 in 40%, HLA-DRB1*0405 in 24% and shared epitope (SE) in 31%. The median delay in starting DMARDs was 24 months. The presence of rheumatoid factor, HLA-DR4 and HLA-DRB1*0405 were not significantly associated with a worse erosive score. Patients who possessed the SE had a higher erosive scores, compared to those who did not (p = 0.05). Concurrently, a delay in starting DMARD was associated with a high erosive score (p = 0.023, r = 0.348). However, after adjustment for the delay in starting DMARD, SE was no longer significantly associated with the erosive score.
CONCLUSIONS:
In these patients, the delay in starting DMARDs had a greater influence on the erosive score than SE alone. Whilst we cannot discount the contribution of the SE presence, we would advocate early usage of DMARDs in every RA patient to reduce joint erosions and future disability.