Anticitrullinated protein antibody ACPA in rheumatoid arthritis: influence of an interaction between HLA-DRB1 shared epitope and a deletion polymorphism in glutathione s-transferasein a cross-sectional studyReportar como inadecuado




Anticitrullinated protein antibody ACPA in rheumatoid arthritis: influence of an interaction between HLA-DRB1 shared epitope and a deletion polymorphism in glutathione s-transferasein a cross-sectional study - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Arthritis Research and Therapy

, 12:R213

First Online: 18 November 2010Received: 02 August 2010Revised: 10 November 2010Accepted: 18 November 2010

Abstract

IntroductionA deletion polymorphism in glutathione S-transferase Mu-1 GSTM1-null has previously been implicated to play a role in rheumatoid arthritis RA risk and progression, although no prior investigations have examined its associations with anticitrullinated protein antibody ACPA positivity. The purpose of this study was to examine the associations of GSTM1-null with ACPA positivity in RA and to assess for evidence of interaction between GSTM1 and HLA-DRB1 shared epitope SE.

MethodsAssociations of GSTM1-null with ACPA positivity were examined separately in two RA cohorts, the Veterans Affairs Rheumatoid Arthritis VARA registry n = 703 and the Study of New-Onset RA SONORA; n = 610. Interactions were examined by calculating an attributable proportion AP due to interaction.

ResultsA majority of patients in the VARA registry 76% and SONORA 69% were positive for ACPA with a similar frequency of GSTM1-null 53% and 52%, respectively and HLA-DRB1 SE positivity 76% and 71%, respectively. The parameter of patients who had ever smoked was more common in the VARA registry 80% than in SONORA 65%. GSTM1-null was significantly associated with ACPA positivity in the VARA registry odds ratio OR, 1.45; 95% confidence interval CI, 1.02 to 2.05, but not in SONORA OR, 1.00; 95% CI, 0.71 to 1.42. There were significant additive interactions between GSTM1 and HLA-DRB1 SE in the VARA registry AP, 0.49; 95% CI, 0.21 to 0.77; P < 0.001 in ACPA positivity, an interaction replicated in SONORA AP, 0.38; 95% CI, 0.00 to 0.76; P = 0.050.

ConclusionsThis study is the first to show that the GSTM1-null genotype, a common genetic variant, exerts significant additive interaction with HLA-DRB1 SE on the risk of ACPA positivity in RA. Since GSTM1 has known antioxidant functions, these data suggest that oxidative stress may be important in the development of RA-specific autoimmunity in genetically susceptible individuals.

AbbreviationsACPAanticitrullinated protein antibody

ACRAmerican College of Rheumatology

APattributable proportion

CIconfidence interval

CYP1a1cytochrome p450 1a1

GSTM1glutathione S-transferase Mu-1

HLAhuman leukocyte antigen

ORodds ratio

PCRpolymerase chain reaction

RArheumatoid arthritis

SEshared epitope

SLEsystemic lupus erythematosus

SONORAStudy of New-Onset Rheumatoid Arthritis

SSOPspecific oligonucleotide probes

VAVeterans Affairs

VARAVeterans Affairs Rheumatoid Arthritis.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3190 contains supplementary material, which is available to authorized users.

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Autor: Ted R Mikuls - Karen A Gould - Kimberly K Bynoté - Fang Yu - Tricia D LeVan - Geoffrey M Thiele - Kaleb D Michaud -

Fuente: https://link.springer.com/







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