Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Genes Immun ; 20(2): 167-171, 2019 02.
Article in English | MEDLINE | ID: mdl-29535371

ABSTRACT

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 4.2, 95% CI: 4-4.5) than AA homozygotes (mean 3.8, 95% CI: 3.7-4) in both the unadjusted (difference = 0.4, p = 0.006) and adjusted analyses (difference = 0.2-0.5, p = 0.002-0.04 depending on the adjustment model). We found no evidence that rs1900693 predicted functional status (BASFI) or global disease scores (BAS-G), and it exerted no influence on either the intention to treat with or efficacy of anti-TNF treatment.


Subject(s)
Multiple Sclerosis/genetics , Polymorphism, Single Nucleotide , Receptors, Tumor Necrosis Factor, Type I/genetics , Spondylitis, Ankylosing/genetics , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Biological Products/therapeutic use , Female , Humans , Male , Middle Aged , Spondylitis, Ankylosing/drug therapy
2.
Nat Genet ; 43(8): 761-7, 2011 Jul 10.
Article in English | MEDLINE | ID: mdl-21743469

ABSTRACT

Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.


Subject(s)
Aminopeptidases/genetics , Aminopeptidases/metabolism , HLA-B27 Antigen/genetics , Peptide Fragments/metabolism , Polymorphism, Genetic/genetics , Spondylitis, Ankylosing/genetics , CARD Signaling Adaptor Proteins/genetics , CD8-Positive T-Lymphocytes/metabolism , Case-Control Studies , Core Binding Factor Alpha 3 Subunit/genetics , Disease Susceptibility , Genome-Wide Association Study , Humans , Interleukin-12 Subunit p40/genetics , Latent TGF-beta Binding Proteins/genetics , Membrane Proteins/genetics , Meta-Analysis as Topic , Minor Histocompatibility Antigens , Receptors, Peptide , Receptors, Prostaglandin E, EP4 Subtype/genetics , Receptors, Tumor Necrosis Factor, Type I/genetics , Spondylitis, Ankylosing/metabolism , White People
SELECTION OF CITATIONS
SEARCH DETAIL
...