Genetic polymorphism of rs9277535 in HLA-DP associated with rheumatoid arthritis and anti-CCP production in a Chinese population

Abstract

HLA-II molecules are critical in triggering human immune response, especially in activating CD4+ T cells. HLA-DP, belonging to HLA-II molecules, draws increasing attention for its role in presentation of viral antigen and autoantigen to T cells. Researches reported single nucleotide polymorphism (SNP) of HLA-DP associated with HBV infection and autoimmune diseases such as SLE. However, little is known about the relationship between HLA-DP and rheumatoid arthritis (RA). Rs9277535 is located in 3' UTR region of HLA-DPB1, a subunit of HLA-DP, and was reported to affect HLA-DP mRNA expression. In the present study, we explored the relationship between gene polymorphism of rs9277535 in HLA-DPB1 and RA susceptibility and progression. Samples from 254 patients with RA and 391 age- and sex-matched healthy controls were collected and genotyped by a polymerase chain reaction-high-resolution melting (PCR-HRM) assay. Serological tests (anti-CCP, rheumatoid factor, C-reactive protein, anti-keratin antibody) were detected by laboratory assays. Strong association was observed between SNP rs9277535 in HLA-DP and RA susceptibility (allele frequency distribution: OR = 1.409, 95%CI = 1.121-1.773, P = 0.004). Further validation was provided by disease model analysis (recessive model: OR = 1.889, 95%CI = 1.194-2.990, P = 0.008; dominant model: OR = 1.464, 95%CI = 1.050-2.041, P = 0.025; additive model: OR = 2.208, 95%CI = 1.335-3.652, P = 0.003). Allele A was correlated to increased risk of RA. Serological test results demonstrated patients carrying allele A of rs9277535 had elevated serum anti-CCP antibody level. The present study provided evidence that HLA-DP gene polymorphism associated with RA susceptibility. Allele A of rs9277535 in HLA-DP correlated to increased risk of RA and elevated serum anti-CCP level.

Characteristics of Gut Microbiota in Patients With Rheumatoid Arthritis in Shanghai, China

“…Meanwhile, the activation of self-reactive CD4+ T cells is necessary, although not sufficient, for inducing autoimmune diseases. HLA-II molecules, especially in activating CD4+ T cells, are critical in triggering human immune response (Huang et al, 2018). Therefore, the regulation of T cell subsets is crucial in maintaining immune balance.…”

HLA-DPB1 rs9277535 polymorphism is associated with rheumatoid arthritis risk in a Chinese Han population

“…Rheumatoid arthritis (RA) is a complex genetic disease associated with many major histocompatibility complex (MHC) genetic factors [ 14 ]. The MHC region is divided into Class I (HLA-A, HLA-B, and HLA-C), Class II (HLA-DRB1, HLA-DQB1, and HLA-DPB1), and Class III (C2 et al) groups [ 15 ]. The Class II HLA-DPB1 gene locus, which encodes proteins that bind to small antigen peptides and carry them into the cell surface for presentation to CD4+ T cells, has crucial effects on the immune system [ 16 ].…”

“…A previous study of 254 Chinese RA patients and 391 control subjects demonstrated that the HLA-DPB1 rs9277535 locus is associated with an increased risk of RA and with elevated serum anti-CCP levels [ 15 ]. However, we found here that the HLA-DPB1 rs9277535 polymorphism was associated with decreased susceptibility to RA in Chinese individuals.…”

Relationship between HLA‐DPA1 genetic polymorphism and anembryonic pregnancy

“…In another study, Hsin-Chou et al found that variants within the rs1431403 region increased the occurrence of rheumatoid arthritis (RA) (Yang et al, 2012). Upregulation of HLA class II expression is an RA clinical detection index, and some studies have shown that the risk of RA is closely related to HLA genetic polymorphism (Guthrie, Gammill, Madeleine, Dugowson, & Nelson, 2011;Huang et al, 2018;Soumya et al, 2012). Based on these findings, it was inferred that rs1431403 polymorphism increased the incidence of anembryonic pregnancy by inducing abnormal expression of HLA class II molecules, such as HLA-DP.…”