Dataset Information

Genetic analysis of TNFST15 variants in ankylosing spondylitis.

ABSTRACT: The purpose of this study was to explore the role of TNF-like ligand 1A (TL1A) gene (TNFST15) polymorphisms (rs3810936, rs7848647, and rs6478109) in the generation of ankylosing spondylitis (AS).Polymerase chain reaction (PCR) and sequencing were used to conduct the genotyping of TNFSF15 polymorphisms in 113 AS patients and 120 healthy persons as the case and control groups. The frequencies comparison was performed by chi-square or t test between the two groups. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to represent the correlation between TNFSF15 polymorphism and AS. Besides, genotypes distribution of the former in controls was checked by Hardy-Weinberg equilibrium (HWE).There was statistically significant difference in AS patients and controls based on family history. Among TNFSF15 polymorphisms, only TT genotype frequency of rs3810936 in cases was obviously high, compared with the controls (P=0.04), the results indicated that TT was a high-risk genotype (OR=2.31, 95% CI=1.03-5.20). However, both of rs6478109, rs7848647 polymorphisms didn't show any association with AS.Rs3810936 of TNFSF15 were related to the risk of AS and we should pay more attention to the role of TNFSF15 polymorphisms in the pathogenesis of AS in the future.

SUBMITTER: Wang NG

PROVIDER: S-EPMC4713654 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Genetic analysis of TNFST15 variants in ankylosing spondylitis.

Wang Nai-Guo NG Wang Feng F Tan Bing-Yi BY Han Shi-Jie SJ Dong Jun J Yuan Ze-Nong ZN Wang Da-Chuan DC

International journal of clinical and experimental pathology 20151101 11

<h4>Aims</h4>The purpose of this study was to explore the role of TNF-like ligand 1A (TL1A) gene (TNFST15) polymorphisms (rs3810936, rs7848647, and rs6478109) in the generation of ankylosing spondylitis (AS).<h4>Methods</h4>Polymerase chain reaction (PCR) and sequencing were used to conduct the genotyping of TNFSF15 polymorphisms in 113 AS patients and 120 healthy persons as the case and control groups. The frequencies comparison was performed by chi-square or t test between the two groups. Odds ...[more]

PMID: 26823868

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Project description:Ankylosing spondylitis (AS) is a common inflammatory arthritic condition. Overt inflammatory bowel disease (IBD) occurs in about 10% of AS patients, and in addition 70% of AS cases may have subclinical terminal ileitis. Spondyloarthritis is also common in IBD patients. We therefore tested Crohn's disease susceptibility genes for association with AS, aiming to identify pleiotropic genetic associations with both diseases. Genotyping was carried out using Sequenom and Applied Biosystems TaqMan and OpenArray technologies on 53 markers selected from 30 Crohn's disease associated genomic regions. We tested genotypes in a population of unrelated individual cases (n = 2,773) and controls (n = 2,215) of white European ancestry for association with AS. Statistical analysis was carried out using a Cochran-Armitage test for trend in PLINK. Strong association was detected at chr1q32 near KIF21B (rs11584383, P = 1.6 × 10(-10), odds ratio (OR)?= 0.74, 95% CI:0.68-0.82). Association with disease was also detected for 2 variants within STAT3 (rs6503695, P = 4.6 × 10(-4). OR = 0.86 (95% CI:0.79-0.93); rs744166, P = 2.6 × 10(-5), OR = 0.84 (95% CI:0.77-0.91)). Association was confirmed for IL23R (rs11465804, P = 1.2 × 10(-5), OR = 0.65 (95% CI:0.54-0.79)), and further associations were detected for IL12B (rs10045431, P = 5.2 × 10(-5), OR = 0.83 (95% CI:0.76-0.91)), CDKAL1 (rs6908425, P = 1.1 × 10(-4), OR = 0.82 (95% CI:0.74-0.91)), LRRK2/MUC19 (rs11175593, P = 9.9 × 10(-5), OR = 1.92 (95% CI: 1.38-2.67)), and chr13q14 (rs3764147, P =?5.9 × 10(-4), OR = 1.19 (95% CI: 1.08-1.31)). Excluding cases with clinical IBD did not significantly affect these findings. This study identifies chr1q32 and STAT3 as ankylosing spondylitis susceptibility loci. It also further confirms association for IL23R and detects suggestive association with another 4 loci. STAT3 is a key signaling molecule within the Th17 lymphocyte differentiation pathway and further enhances the case for a major role of this T-lymphocyte subset in ankylosing spondylitis. Finally these findings suggest common aetiopathogenic pathways for AS and Crohn's disease and further highlight the involvement of common risk variants across multiple diseases.

Project description:We have compared synovial biopsies from ankylosing spondylitis and undifferentiated spondylitis patients with healthy controls and osteoarthritis patients Objective: In spondylarthropies, whole-genome gene expression profiling studies have been limited to peripheral blood to date. By undertaking a study in knee synovial biopsies from spondylarthropy (SpA) and ankylosing spondylitis (AS) patients we aimed to identified joint-specific candidate genes and pathways. These pathways may mediate systemic inflammation driven joint damaging processes and more specifically, the osteoproliferation that is characteristic of these conditions. Methods: RNA was extracted from six seronegative SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: 416 differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, osteoblast activity, B-cell associated, matrix catabolic, and metabolic pathways. The inflammatory mediator, MMP3, was strongly upregulated in AS/SpA samples and the Wnt pathway inhibitors DKK3 and Kremen1 were downregulated. Conclusion: Pathways mediating both systemic inflammation as well as local tissue changes were identified. This suggests initial systemic inflammation in spondylarthropies transfers to and persists in the local joint environment, subsequently mediating changes in genes directly involved in the destructive tissue remodelling. Fifteen knee synovial biopsy tissue samples consisting of six seronegative spondyloarthropy (SpA), two ankylosing spondylitis (AS), three osteoarthritis (OA) and four normal control biopsies were obtained from the Synovial Tissue Bank at the Repatriation General Hospital in Adelaide, South Australia with the appropriate ethical approval (Supplementary Table 1). All patients provided informed written consent.

Dataset Information

Genetic analysis of TNFST15 variants in ankylosing spondylitis.

Publications

Genetic analysis of TNFST15 variants in ankylosing spondylitis.

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