Genetic polymorphisms of G protein-coupled receptor 65 gene are associated with ankylosing spondylitis in a Chinese Han population: A case-control study

ObjectiveThis study aimed to assess the association between two tag single nucleotide polymorphisms (SNPs) (rs68177277 and rs11624293) of G protein-coupled receptor 65 (GPR65) gene and ankylosing spondylitis (AS) susceptibility in a Chinese Han population.Methods673 patients with AS diagnosed according to the modified New York criteria and 679 age- and gender-matched healthy controls were recruited. SNP genotyping for rs68177277 and rs11624293 polymorphisms were performed using the SNPscan technique. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).ResultsGenotype and allele distribution of rs11624293 but not rs68177277 were significantly different between AS and controls (p = 0.004 and p = 0.002). Compared to the wild-type T/T genotype and T allele at rs11624293, the frequencies of C/T genotype and C allele were significantly higher in AS than controls after adjusting for age and gender (OR = 1.527, 95%CIs: 1.190–1.958; OR = 1.515, 95%CIs: 1.183–1.942, respectively). Dominant and co-dominant model of rs11624293 were predictive of AS susceptibility. In AS patients, the genotype of rs11624293 was significantly associated with BASFI scores in those with low disease activity (BASDAI < 4, p = 0.007).ConclusionsThe results of our study suggest that rs11624293 polymorphism of GPR65 gene is associated with the susceptibility and severity of AS in Chinese Han population.     

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

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.     

Increased expression of TIPE2 mRNA in PBMCs of patients with ankylosing spondylitis is negatively associated with the disease severity

Ankylosing spondylitis (AS) is an autoimmune disease and characterized by chronic inflammatory arthritis. Tumor necrosis factor α induced protein-8 like-2 (TIPE2) is responsible for maintaining immune homeostasis by inhibiting the secretion of inflammatory cytokines in the condition of inflammation. However, whether TIPE2 participates in the development of AS remains unknown. In this study, we measured the mRNA expression of TIPE2 and TIPE1 in peripheral blood mononuclear cells (PBMCs) from 45 AS patients and 40 healthy controls by qRT-PCR. The results showed TIPE2 expression was significantly increased in AS patients compared with controls (P=0.0066), while there was no significant difference for TIPE1 between two groups (P = 0.2302). Moreover, the expression of TIPE2 mRNA in AS patients were decreased after treatment with TNF-α blocker (P < 0.001). In addition, we found that TNF-α or plasma from AS patients induced TIPE2 expression in THP-1 cells in vitro. More importantly, the TIPE2 mRNA expression levels were negatively correlated with TNF-α, hsCRP and bath ankylosing spondylitis disease activity index (BASDAI) (r = ?0.3574, P = 0.0159; r = ?0.3174, P = 0.0336; r = ?0.6000, P < 0.0001; respectively) in the AS patients. These results indicated that TIPE2 contributes to the pathogenesis of AS.     

Association of the HLA‐B27 antigen and the CTLA4 gene CT60/rs3087243 polymorphism with ankylosing spondylitis in Algerian population: A case–control study

Ankylosing spondylitis (AS) is a complex inflammatory disease that represents a major health problem both in Algeria and worldwide. Several lines of evidence support that genetic risk factors play a role in AS etiology and the CTLA4 gene has attracted a considerable attention. In this study, we were interested in evaluating the HLA‐B27 frequency and in exploring the CTLA4 gene in a sample of the North African population. The dataset of the current study is composed of 81 patients with AS and 123 healthy controls. All samples were genotyped by TaqMan^®allelic discrimination assay. The genetic risk of the HLA‐B27 specificity and the CTLA4/CT60 polymorphism were assessed by odds ratios (OR) with 95% confidence intervals (CI). High spondylitis risk was detected for HLA‐B27 allele (OR= 14.62, p = 10^?6) in addition to a significant association of the CT60*G allele (OR= 1.89, p = .002). After gender and age stratifications, the association of the CT60*G allele was still significant in females sample (OR= 2.10, p = .001) and when age up to 30 years (OR = 2.21, p = .008). Interestingly, the CT60*G allele revealed an increased spondylitis risk in the B27 negative group (OR= 2.81, p = .006). The present work showed in West Algerian population that the HLA‐B27 antigen and the variation in the CTLA4 3′UTR region played an important role in the ankylosing spondylitis susceptibility. The heterogeneity of this disease is deduced by genetic difference found between B27+ and B27? groups.