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National Institute for Health Research ... Publications | LitMetric

8 results match your criteria: "National Institute for Health Research Oxford Comprehensive Biomedical Research Centre[Affiliation]"

Ankylosing Spondylitis (AS) is a common form of inflammatory spinal arthritis with a complex aetiology and high heritability, involving more than 100 genetic associations. These include several AS-associated single nucleotide polymorphisms (SNPs) upstream of which encodes the multifunctional RUNT-related transcription factor (TF) 3. The lead associated SNP ( = 2.

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Genetic polymorphism (rs1800693) of TNFRSF1A (type 1 tumour necrosis factor receptor) encodes a potentially anti-inflammatory soluble truncated form of the p55 receptor, which is associated with predisposition to multiple sclerosis but protection against ankylosing spondylitis (AS). We analysed 2917 UK Caucasian cases by linear and logistic regression for associations of rs1800693 with disease severity assessed by the Bath Ankylosing Spondylitis measures of disease activity and function (BASDAI, BAS-G and BASFI) and/or responses to anti-TNF therapy. In contrast to predictions, rs1800693 GG homozygotes actually had significantly worse BASDAI (mean 4.

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Evidence for a second ankylosing spondylitis-associated regulatory polymorphism.

RMD Open

February 2018

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Objectives: To explore the functions of single nucleotide polymorphisms (SNPs) associated with ankylosing spondylitis (AS).

Methods: Individual SNP associations were evaluated in 4230 UK cases. Their effects on transcription factor (TF) binding, transcription regulation, chromatin modifications, gene expression and gene interactions were tested by database interrogation, luciferase reporter assays, electrophoretic mobility gel shifts, chromatin immunoprecipitation and real-time PCR.

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Investigation of a possible extended risk haplotype in the IL23R region associated with ankylosing spondylitis.

Genes Immun

March 2017

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Nuffield Orthopaedic Centre, Oxford, UK.

The IL23R region on chromosome 1 exhibits complex associations with ankylosing spondylitis (AS). We used publicly available epigenomic information and historical genetic association data to identify a putative regulatory element (PRE) in the intergenic region between IL23R and IL12RB2, which includes two single-nucleotide polymorphisms (SNPs) independently associated with AS-rs924080 (P=2 × 10) and rs11578380 (P=2 × 10). In luciferase reporter assays, this PRE showed silencer activity (P<0.

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ERAP1 association with ankylosing spondylitis is attributable to common genotypes rather than rare haplotype combinations.

Proc Natl Acad Sci U S A

January 2017

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, United Kingdom;

We investigated the proposal that ankylosing spondylitis (AS) is associated with unusual ERAP1 genotypes. ERAP1 haplotypes were constructed for 213 AS cases and 46 rheumatoid arthritis controls using family data. Haplotypes were generated from five common ERAP1 single nucleotide polymorphisms (SNPs)-rs2287987 (M349V), rs30187 (K528R), rs10050860 (D575N), rs17482078 (R725Q), and rs27044 (Q730E).

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The genetic association of RUNX3 with ankylosing spondylitis can be explained by allele-specific effects on IRF4 recruitment that alter gene expression.

Ann Rheum Dis

August 2016

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK National Institute for Health Research Oxford Musculoskeletal Biomedical Research Unit, Oxford, UK National Institute for Health Research Oxford Comprehensive Biomedical Research Centre, Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford, UK.

Objectives: To identify the functional basis for the genetic association of single nucleotide polymorphisms (SNP), upstream of the RUNX3 promoter, with ankylosing spondylitis (AS).

Methods: We performed conditional analysis of genetic association data and used ENCODE data on chromatin remodelling and transcription factor (TF) binding sites to identify the primary AS-associated regulatory SNP in the RUNX3 region. The functional effects of this SNP were tested in luciferase reporter assays.

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Ankylosing spondylitis is associated with the anthrax toxin receptor 2 gene (ANTXR2).

Ann Rheum Dis

November 2014

National Institute for Health Research Oxford Comprehensive Biomedical Research Centre, University of Oxford, Oxford, UK National Institute for Health Research Oxford Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK.

Objectives: ANTXR2 variants have been associated with ankylosing spondylitis (AS) in two previous genome-wide association studies (GWAS) (p∼9×10(-8)). However, a genome-wide significant association (p<5×10(-8)) was not observed. We conducted a more comprehensive analysis of ANTXR2 in an independent UK sample to confirm and refine this association.

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