Variation at HLA‐DPB1 is associated with dermatomyositis in Chinese population

Abstract

Dermatomyositis (DM) is a polygenic disorder characterized by inflammation of skeletal muscle and skin. To date, the exact etiopathogenesis of DM remains elusive. To explore the genetic basis of DM, we conducted genome-wide genotyping analysis of 127 patients and 1566 healthy controls by Illumina Human OmniZhongHua-8 BeadChips in the Chinese Han population. We investigated whether the three SNP (rs7750458, rs9501251 and rs9500928) at 6p21.32 in the HLA-DPB1 gene were significantly associated with DM (P < 5 × 10 ) and identified two susceptibility loci at 7q34 (PIP, rs9986765, P = 7.45 × 10 , odds ratio [OR] = 2.71) and 10q24.2 (CPN1, rs3750716, P = 9.04 × 10 , OR = 4.39) with suggestive evidence. We imputed 6674 classical human leukocyte antigen (HLA) alleles, amino acids and SNP from the discovery dataset, and stepwise analysis revealed that HLA-DPB1*17 in class II HLA genes were significantly associated with DM susceptibility. This study represents the first genome-wide association study (GWAS) of DM in the Chinese Han population. For the first time, HLA-DPB1 was found to be associated with DM in this population. Moreover, we identified two novel suggestive susceptibility loci (PIP and CPN1) and confirmed four previously reported genes (DMB, DQA1, DQB1 and DRB1) having potential associations with DM in the Chinese Han population. Our GWAS results in this population should provide important information regarding the genetic etiopathogenesis of DM and facilitate the development of new therapies for the treatment of DM and the prevention of DM progression.

The MHC locus and genetic susceptibility to autoimmune and infectious diseases

“…After the development of wide-screen genotyping platforms and imputation pipelines, MHC imputation and fine-mapping were performed in European and Asian populations for most common autoimmune diseases, including RA [19, 25, 33, 34], CeD [35], psoriasis [36], ankylosing spondylitis (AS) [37], systemic lupus erythematosus (SLE) [33, 38–41], T1D [42, 43], multiple sclerosis (MS) [44, 45], Graves’ disease [24], inflammatory bowel disease (IBD) [46], and dermatomyositis (DM) [47]. Table 1 shows the main associated variants and independently associated loci for autoimmune diseases.…”

“…Similarly, the main associations were determined for T1D, MS, and SLE within the MHC class II locus (the associations for these three diseases are to a particular HLA-DQ-DR haplotype), and there are also independent, but weaker associations with the class I and/or III regions. In DM, fine mapping in an Asian population identified MHC associations driven by variants located around the MHC class II region, with HLA-DP1*17 being the most significant [47]. In contrast, the primary and strongest associations in psoriasis and AS were to MHC class I molecules, while independent associations to the class I locus were also reported for IBD and Graves’ disease.…”

Positive Association betweenANKRD55Polymorphism 7731626 and Dermatomyositis/Polymyositis with Interstitial Lung Disease in Chinese Han Population

“…It would, therefore, be advantageous to investigate the biomarkers associated with the development of ILD in patients with DM/PM. To date, several genetic [10–12] and environmental [13–16] factors have been proposed to contribute to the development of DM/PM. However, these identified predisposing factors are unable to completely account for the pathogenesis of DM/PM.…”

Correlation analysis of the HLA‐DPB1*05:01 and BTNL2 genes within the histocompatibility complex region with a clinical phenotype of psoriasis vulgaris in the Chinese Han population

“…In our previous study, we sequenced the MHC region of 9946 Chinese Han patients with geographically matched psoriasis and then investigated the significance of gene polymorphisms in the HLA‐DPB1 and BTNL‐2 genes in which MHC was found to be associated with psoriasis . HLA‐DPB1 encoded the HLA‐DPB‐chain, which forms heterodimers with DPA1 on the cell surface and presents antigens to CD4‐positive T lymphocytes . These CD4 T cells infiltrated the perivascular or the interfascicular and the area around the fascicles, which may contribute to inflammatory or autoimmune diseases, such as type 1 diabetes, systemic sclerosis, chronic hepatitis B infection, rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus, It was reported that three single nucleotide polymorphims at 6p21.32 in the HLA‐DPB1 gene were significantly associated with diabetes mellitus in the Chinese Han population .…”