Dataset Information

Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis.

ABSTRACT: To examine the association of previously identified autoimmune disease susceptibility loci with granulomatosis with polyangiitis (Wegener's) (GPA), and to determine whether the genetic susceptibility profiles of other autoimmune diseases are associated with those of GPA.Genetic data from 2 cohorts were meta-analyzed. Genotypes for 168 previously identified single-nucleotide polymorphisms (SNPs) associated with susceptibility to different autoimmune diseases were ascertained in a total of 880 patients with GPA and 1,969 control subjects of European descent. Single-marker associations were identified using additive logistic regression models. Associations of multiple SNPs with GPA were assessed using genetic risk scores based on susceptibility loci for Crohn's disease, type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis (RA), celiac disease, and ulcerative colitis. Adjustment for population substructure was performed in all analyses, using ancestry-informative markers and principal components analysis.Genetic polymorphisms in CTLA4 were significantly associated with GPA in the single-marker meta-analysis (odds ratio [OR] 0.79, 95% confidence interval [95% CI] 0.70-0.89, P = 9.8 × 10(-5) ). The genetic risk score for RA susceptibility markers was significantly associated with GPA (OR 1.05 per 1-unit increase in genetic risk score, 95% CI 1.02-1.08, P = 5.1 × 10(-5) ).RA and GPA may arise from a similar genetic predisposition. Aside from CTLA4, other loci previously found to be associated with common autoimmune diseases were not statistically significantly associated with GPA in this study.

SUBMITTER: Chung SA

PROVIDER: S-EPMC3425721 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis.

Chung Sharon A SA Xie Gang G Roshandel Delnaz D Sherva Richard R Edberg Jeffrey C JC Kravitz Megan M Dellaripa Paul F PF Hoffman Gary S GS Mahr Alfred D AD Seo Philip P Specks Ulrich U Spiera Robert F RF St Clair E William EW Stone John H JH Plenge Robert M RM Siminovitch Katherine A KA Merkel Peter A PA Monach Paul A PA

Arthritis and rheumatism 20121001 10

<h4>Objective</h4>To examine the association of previously identified autoimmune disease susceptibility loci with granulomatosis with polyangiitis (Wegener's) (GPA), and to determine whether the genetic susceptibility profiles of other autoimmune diseases are associated with those of GPA.<h4>Methods</h4>Genetic data from 2 cohorts were meta-analyzed. Genotypes for 168 previously identified single-nucleotide polymorphisms (SNPs) associated with susceptibility to different autoimmune diseases were ...[more]

PMID: 22508400

Similar Datasets

Project description:The objective of this study is to assess the relationship between inflammatory disease in granulomatosis with polyangiitis (GPA, Wegener's) and the development of subclinical atherosclerosis. A total of 46 adult patients with GPA were enrolled. Disease status was measured by Birmingham vasculitis assessment scores as modified for GPA, vasculitis damage index, disease duration, and number of relapses. Classic atherosclerotic risk factors, platelet aggregation responses, and circulating microparticle (MP) levels were recorded. All patients underwent carotid artery intima-media thickness (IMT) measurement as outcome for subclinical atherosclerosis. In univariate analyses, systolic and diastolic blood pressure, creatinine, and age were significantly associated with higher IMT (ρ values 0.37, 0.38, 0.35, and 0.054, respectively [P < 0.02 for all]). In a multiple regression model, greater number of relapses, older age at the onset of disease, and higher diastolic blood pressure were found to be associated with higher IMT (P values 0.003, <0.001, and 0.031, respectively). MP counts and platelet reactivity correlated well with disease activity in GPA. Furthermore, MPs were found to activate vascular endothelial cells and platelets in vitro. The cumulative burden of systemic inflammation in GPA correlated with the development of subclinical atherosclerosis. The correlation with subclinical atherosclerosis could be because of glucocorticoid use and not the inflammatory process in GPA, giving the inherent bias that exits with the use of glucocorticoid with each relapse. The findings of increased levels of circulating leukocyte-derived MPs and enhanced platelet reactivity during relapse suggest possible roles for MPs and platelets in disease pathogenesis and support a growing literature that links inflammation, atherosclerosis, and platelet activation. This hypothesis is further substantiated by our demonstration that MPs isolated from plasma of GPA patients can activate platelets and vascular endothelial cells.

Dataset Information

Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis.

Publications

Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets