Genetic Polymorphisms of rs3077 and rs9277535 in HLA-DP associated with Systemic lupus erythematosus in a Chinese population

Junlong Zhang,Anning Tian,Bei Cai,Yun Liao,Lanlan Wang,Lin Chen,Bin Yang,Wenli Zhan,Yongkang Wu

doi:10.1038/srep39757

Abstract

Although the SLE risk gene loci of HLA-DR and HLA-DQ within the major histocompatibility complex (MHC) region has been gradually revealed by recent Genome-Wide Association studies (GWAS), the association of HLA-DP polymorphisms with SLE was minimally reported. Considering that the variants in rs3077 and rs9277535 in the HLA-DP region could influence the immune response by affecting antigen presentation of HLA class II molecules to CD4+ T cells, the present study aimed to explore the role of HLA-DP polymorphisms in SLE. In total, samples from 335 SLE patients and 635 healthy controls were collected and genotyped by a polymerase chain reaction-high resolution melting (PCR-HRM) assay. A significant positive correlation was observed between the SNP rs3077, rs9277535 of HLA-DP and SLE susceptibility (rs3077, OR = 0.74, 95%CI = 0.60–0.91, P = 0.004; rs9277535, OR = 0.72, 95%CI = 0.59–0.88, P = 0.001). Rs3077 polymorphism was corelated to IL-17, INF-γ and cutaneous vasculitis (P = 0.037, P = 0.020 and P = 0.006, respectively). Additionally, rs3077 AA genotype carriers showed lower concentration of inflammatory cytokines and lower cutaneous vasculitis incidence than did the other two genotype. No significant association was observed between rs9277535 and cytokines or any clinical features. In conclusion, HLA-DP polymorphisms (rs3077 and rs9277535) were associated with SLE susceptibility and the levels of some inflammatory cytokines in SLE patients.

Highlights

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder characterized by a lack of tolerance to self-antigens and the hyper production of multiple pathogenic autoantibodies and immune complexes, which result in systemic inflammation and damage to multiple organ systems[1]
Considering that a number of studies have revealed that HLA-DP genes were associated with susceptibility to many autoimmune diseases, including Wegener’s granulomatosis, systemic sclerosis, multiple sclerosis and others[18,19,20], HLA-DP polymorphisms are likely to play an important role in SLE
We found two SNPs, rs3077 and rs9277535 of HLA-DP, did associate with the SLE susceptibility and the A allele of the two SNPs are potential protective allele in SLE in the Chinese Han population

Summary

Introduction

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder characterized by a lack of tolerance to self-antigens and the hyper production of multiple pathogenic autoantibodies and immune complexes, which result in systemic inflammation and damage to multiple organ systems[1]. The long-range linkage disequilibrium (LD) within the MHC region makes the disease susceptibility contribution of each component gene difficult to assess, overwhelming evidence confirmed that the genetic variants in HLA-DR and HLA-DQ are predisposed to SLE14,15. HLA-DPB1*05:01 was reported relating to the presence of autoantibodies in Japanese SLE patients[17] These studies neither have found the role of allele variants on HLA-DPA1 nor have explored the further association between the reported SNPs and the process of SLE. Considering that a number of studies have revealed that HLA-DP genes were associated with susceptibility to many autoimmune diseases, including Wegener’s granulomatosis, systemic sclerosis, multiple sclerosis and others[18,19,20], HLA-DP polymorphisms are likely to play an important role in SLE.

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Conclusion