Association study of copy number variants in CCL3L1, FCGR3A and FCGR3B genes with risk of ankylosing spondylitis in a West Algerian population

Abstract

Numerous single nucleotide polymorphisms (SNPs) were explored in the Algerian population to evaluate associated ankylosing spondylitis (AS) genetic risk factors, but no study has identified the impact of copy number variations (CNVs). The aim of the study was to determine whether CNVs of CCL3L1, FCGR3A and FCGR3B genes were also associated with the susceptibility of AS disease in Algerian population. The data set of the current study is composed of 81 patients with AS and 119 healthy controls. All samples were genotyped by digital droplet PCR (ddPCR). Chi‐square test and OR calculation were used to evaluate association between CNVs and AS and the risk associated with copy numbers (CN). In results, FCGR3A CN less than two copies (<2) was significantly increased in spondylitis patients (p = .0001, OR = 7.74 [2.32–25.74]). Additionally, FCGR3A CN < 2 copies association was present only in HLA‐B27 (‐) patients. We have concluded that FCGR3A deletions have an independent effect on AS regarding HLA‐B27 status. This is the first study that investigated the CCL3L1 CNVs in relation to AS risk disease. It reveals that CCL3L1 and FCGR3B CNVs may not be involved in susceptibility to AS risk in the Algerian population.

Identification of novel genes in Behcet’s disease using integrated bioinformatic analysis

“…The FCGR3B gene encodes FCGRIIIb (also known as CD16b), specifically expressed on neutrophils [42]. Previous studies demonstrated that FCGR3 gene copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) are associated with several diseases, especially autoimmune disorders, such as systemic lupus erythematosus [43][44][45], rheumatoid arthritis [45], ANCAassociated systemic vasculitis (AASV) [43,46,47], sarcoidosis [48,49], and others [50]. Few hypotheses suggest that FCGRIIIb is primarily expressed on neutrophils, and hence its deficiency or variation may obstruct the clearance of immune complexes by neutrophils and enhance the proinflammatory effect [47].…”

An Update Evolving View of Copy Number Variations in Autoimmune Diseases

“…Wang et al (2016) found that AS patients had low copies (&3) of FCGR3A and FCGR3B in the Chinese population, implying that a lower copy number of these two genes confers risk for the susceptibility of AS. The study of Dahmani et al (2019) found that the proportion of AS patients with less than two copies of FCGR3A was higher in the Algerian population and that less than two copies of FCGR3A was only associated with HLA-B27-negative AS patients, suggesting that FCGR3A deletion has an independent effect on AS regarding HLA-B27 status. Their results also showed that CCL3L1 and FCGR3B CNVs may not be involved in the predisposition of AS in the Algerian population (Dahmani et al, 2019).…”

“…The study of Dahmani et al (2019) found that the proportion of AS patients with less than two copies of FCGR3A was higher in the Algerian population and that less than two copies of FCGR3A was only associated with HLA-B27-negative AS patients, suggesting that FCGR3A deletion has an independent effect on AS regarding HLA-B27 status. Their results also showed that CCL3L1 and FCGR3B CNVs may not be involved in the predisposition of AS in the Algerian population (Dahmani et al, 2019). Wang et al (2018) found that one copy of TLR7 was related to AS in the Chinese population after Bonferroni correction and adjustment of age and sex, and less than one copy of TLR7 confers risk for AS susceptibility in male patients, but is a protective factor in female AS patients.…”