DRB1*04 subtype in Thai patients with rheumatoid arthritis.
ABSTRACT Rheumatoid arthritis (RA) in a Thai population is significantly associated with HLA-DR4. The frequency of DR4 was 43 per cent in RA patients and 20 per cent in the healthy controls (p = 0.00008, OR = 3.06, 95% CI = 1.71, 5.52). To analyze which DR4 alleles were associated with the disease, the authors subtyped 52 DR4-positive RA patients compared to 28 DR4-positive healthy controls by amplification with DR4-specific primers followed by direct sequencing. Six DR4 alleles (DRB1*0401, *0403, *0404, *0405, *0406, and *0410) were found in the RA patient group while 5 alleles (DRB1*0401, *0403, *0405, *0406, and *0407) were found in the control group. Both groups were predominated by DRB11*0405, but there was a significant increase in the frequency of DRB1*0405 in DR4+ RA patients compared to DR4+ healthy controls (84.6% vs 46.4%, p = 0.0008, OR = 6.35, 95% CI = 1.96, 21.08). DR4 which shared epitope alleles (DRB1*0401, *0404, *0405) were observed in 47 (90.3%) DR4+ patients and 15 (53.5%) DR4+ controls (p = 0.0005, OR = 8.15, 95% CI = 2.29, 33.2). In addition, the authors found that DRB1*0403 was significantly decreased in DR4+ RA patients compared to controls (p = 0.0065, OR = 0.07, 95% CI = 0, 0.67).
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ABSTRACT: To investigate the associations between HLA-DRB1 shared epitope (SE) alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia. 1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA) and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping. The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups. The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.PLoS ONE 01/2011; 6(6):e21069. · 3.73 Impact Factor
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ABSTRACT: The aim of this study is to explore relationship between HLA-DRB1 alleles and the susceptibility and clinical features of rheumatoid arthritis (RA) in the south Tunisian population. We studied 142 RA patients and 123 controls matched for age, sex, and ethnicity. HLA-DRB1 genotyping and HLA-DRB1*04 subtypes were performed using polymerase chain reaction/sequence-specific primers. Association was assessed based on the χ (2) test and odds ratio with 95% confidence interval. For multiple comparisons, p value was corrected (p (c)) with Bonferroni test. Two alleles, HLA-DRB1*04 (p=0.045, p(c)=NS) and HLA-DRB1*10 (p=0.021, p(c)=NS), were found to have increased frequencies in RA patients compared to controls. In contrast HLA-DRB1*08 allele was found to have a decreased frequency in patients compared to controls (p=0.044, p(c)=NS). Molecular subtyping of the most prevalent allele (DRB1*04) revealed increased frequencies of HLA-DRB1*04:05 in patients compared to controls (p=0.013, p(c)=NS) whereas HLA-DRB1*04:02 showed a protective effect (p=0.005, p(c)=0.04). Moreover, stratified analyses indicated statistically significant associations between HLA-DRB1*04 allele and anti-cyclic peptides antibodies positivity (ACPA(+)) and rheumatoid factor positivity (RF(+); p(c)=0.03, for both subgroups), HLA-DRBI*10 and ACPA(+) and the presence of another autoimmune disease (p(c)=0.05 and p(c)=0.007, respectively), and HLA-DRB1*04:05 and RF(+) and erosion (p(c)=0.005 and p(c)=0.049; respectively). A significant decrease in the frequency of the DRB1*04:02 allele was observed in patients with ACPA(+) and RF(+) subgroups (p(c)=0.04 and p(c)=0.02, respectively). Our results showed that there was a trend of positive association of HLA-DRB1*04 and HLA-DRB1*10 with RA as such and significant associations with the disease severity in the south Tunisian population.Clinical Rheumatology 02/2012; 31(6):937-42. · 2.04 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA) in Thai population is significantly associated with HLA-DR4 shared epitope (SE) alleles, particularly with DRB1*0405 (P = 0.00004, OR = 3.84, 95% CI = 1.93, 7.7). In addition, tumor necrosis factor-alpha (TNF-alpha) gene -863A alleles were found to be significantly increased in 77 RA patients compared to 162 healthy controls (P = 0.03, OR = 1.73, 95% CI = 1.05, 2.87). Interestingly, TNF-863 AC and SE have a synergistic effect on the susceptibility to RA. The OR for the presence of both risk factors (DR4 SE and -863 AC) was cumulative: 15.4 (95% CI = 3.75, 73.6) while the separate OR of DR4 SE and -863 AC were 3.84 and 2.36, respectively. The TNF was not associated with the clinical manifestation and severity of Thai RA patients. However, a highly significant association was found between RF positivity, one marker for severity, and RA patients with DR4 SE (P = 0.0005, OR = 9.42, 95% CI = 2.26, 45.27).Rheumatology International 01/2008; 28(2):161-5. · 2.21 Impact Factor