HLA-DRB1 Shared Epitope-Dependent DR-DQ Haplotypes Are Associated with Both Anti-CCP–Positive and –Negative Rheumatoid Arthritis in Chinese Han

Abstract

The association between Human Leukocyte Antigen (HLA) class II and rheumatoid arthritis (RA) has been extensively studied, but few reported DR-DQ haplotype. Here we investigated the association of HLA-DRB1, DQA1, DQB1, and DR-DQ haplotypes with RA susceptibility and with anti-CCP antibodies in 281 RA patients and 297 control in Han population. High-resolution genotyping were performed. The HLA-DRB1 shared epitope (SE)-encoding allele *0405 displayed the most significant RA association (P = 1.35×10−6). The grouped DRB1 SE alleles showed great association with RA (P = 3.88×10−13). The DRB1 DRRAA alleles displayed significant protective effects (P = 0.021). The SE-dependent DR-DQ haplotype SE-DQ3/4/5 remained strong association with both anti-CCP -positive (P = 3.71×10−13) and -negative RA (P = 3.89×10−5). Our study revealed that SE alleles and its haplotypes SE-DQ3/4/5 were highly associated with RA susceptibility in Han population. The SE-DQ3/4/5 haplotypes were associated with both anti-CCP positive RA and -negative RA.

HLA‐DRB1 gene polymorphisms and its associations with rheumatoid arthritis in Chinese Han women of Shaanxi province, northwest of China

“…For instance, Liu et al . reported that significant RA association was observed with HLA‐DRB1*04:05 when compared with healthy controls in Han Chinese originated from the region of northern China (Liu et al ., ). Yang et al .…”

“…Moreover, this study found that the AF of SE (DRB1*01:01; 01:02; 04:01; *04:04; *04:05; *04:10 and *10:01) demonstrated an increasing trend in Chinese Han population RA patients in Shaanxi province. This result is consistent with several previous studies (Kurko et al ., ; Liu et al ., ; Louthrenoo et al ., ). Our findings further supported the SE hypothesis which described the associations between HLA‐DRB1 and RA (Liu et al ., ).…”

“…This study found that the AF of HLA‐DRB1* 04:05 were significant higher in patients with RA of Chinese Han population resided in Shaanxi province. Some studies have reported that HLA‐DRB1* 04:05 might be a major risk factor for RA in other Chinese population (Liu et al ., ; Yang et al ., ). For instance, Liu et al .…”

“…This result is consistent with several previous studies (Kurko et al ., ; Liu et al ., ; Louthrenoo et al ., ). Our findings further supported the SE hypothesis which described the associations between HLA‐DRB1 and RA (Liu et al ., ). Some studies have shown that the presence of SE alleles is associated with the severity of RA and extra‐articular manifestations (Del Rincon et al ., ; Turesson et al ., ).…”

Genetic markers and clinical relevance in rheumatoid arthritis

“…[2][3][4] The SEdependent DR-DQ haplotype SE-DQ3/4/5 remained in strong association with both ACPA -positive and -negative RA in a Han population. 5 A recent study identified a novel association at amino acid position 77 in HLA-A with ACPA-positive RA. 6 The interaction between the presence of double copies of DRb1-SE alleles and smoking increased a great risk for development of RA.…”