Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune diseases characterized by inflammation and destruction of small-sized vascular walls in conjunction with ANCA. The main antigens targeted by ANCA are myeloperoxidase (MPO) and proteinase 3 (PR3). AAV comprises microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA) [1]. AAV is a relatively rare disease, the estimated incidence rates in China is 0.25 ‰ [2]. The incidence of AAV increases with age, and shows a clear female dominance in most published studies [3]. There is a preponderance of MPA in Chinese patients with AAV rather than GPA and EGPA, and most MPA patients are positive for MPO-ANCA. In addition, Ethnic variation also affects the incidence rate of AAV in China, with Dong ethnic people being the highest frequency [2].

Along with environmental and immune systemic contributions, genome-wide association studies (GWAS) conducted in European populations has identified genetic factors in the pathogenesis of AAV. However, GWAS in Asian population has not been reported. In Japanese patients, HLA-DRB1*0901 is reported to be associated with MPA and MPO-ANCA positive vasculitis [4]. A study on Chinese population detects that HLA-DRB1*1101 could be a risk factor for MPA [5]. In recent years, we have found some autophagy related gene (ATG) polymorphisms associated with MPA in Guangxi population in China [6], [7]. In different population, the genetic loci related to AAV are different. Therefore, it is difficult to explore the genetic polymorphisms associated with AAV risk in populations with different genetic backgrounds.

Casitas B-lineage lymphoma (CBL), a membership of Cbl family, encodes an E3 ubiquitin ligase and negatively regulates various signaling pathways [8], [9], [10]. In human, Cbl protein family includes three members, CBL (also known c-CBL), CBL-B and CBL-C [11]. Some studies have explored the role of CBL protein in immune regulation, involving immune tolerance, control of T-cell signal transduction, B-cell development and dendritic cell maturation [12], [13], [14]. Our previous research found that MPA plasma derived exosomal miR-1287-5p induces endothelial inflammatory injury and neutrophil adhesion by targeting CBL [15]. CBL also plays a negative role in regulating autophagy via failing to mediate the autophagic targeting of Src [16]. As an autoimmune disease, dysfunction of immune cells and autophagy has been found in AAV patients [17], [18], so we speculate that CBL gene may play a potential role in the occurrence and development of AAV. The association between CBLB polymorphism and the risk of multiple sclerosis has been reported [19]. However, it remains unknown whether CBL genetic polymorphisms is related to the risk of AAV. Considering that MPA is the main clinical phenotype in China, this study enrolled MPA patients and selected five candidate CBL single nucleotide polymorphisms (SNPs) to evaluate the association between CBL SNPs and MPA risk in Guangxi population of China.