21 research outputs found
Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy.
No full textGiant cell arteritis (GCA) and Takayasu’s arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus
Corrigendum: Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy.
No full textGiant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus
Cross-phenotype analysis of Immunochip data identifies <i>KDM4C</i> as a relevant <i>locus</i> for the development of systemic vasculitis
No full textObjetiveSystemic vasculitides represent a heterogeneous group of rare complex diseases of the blood vessels with a poorly understood aetiology. To investigate the shared genetic component underlying their predisposition, we performed the first cross-phenotype meta-analysis of genetic data from different clinically distinct patterns of vasculitis.MethodsImmunochip genotyping data from 2465 patients diagnosed with giant cell arteritis, Takayasu’s arteritis, antineutrophil cytoplasmic antibody-associated vasculitis or IgA vasculitis as well as 4632 unaffected controls were analysed to identify common susceptibility loci for vasculitis development. The possible functional consequences of the associated variants were interrogated using publicly available annotation data.ResultsThe strongest association signal corresponded with an intergenic polymorphism located between HLA-DQB1 and HLA-DQA2 (rs6932517, P=4.16E-14, OR=0.74). This single nucleotide polymorphism is in moderate linkage disequilibrium with the disease-specific human leucocyte antigen (HLA) class II associations of each type of vasculitis and could mark them. Outside the HLA region, we identified the KDM4C gene as a common risk locus for vasculitides (highest peak rs16925200, P=6.23E-07, OR=1.75). This gene encodes a histone demethylase involved in the epigenetic control of gene expression.ConclusionsThrough a combined analysis of Immunochip data, we have identified KDM4C as a new risk gene shared between systemic vasculitides, consistent with the increasing evidences of the crucial role that the epigenetic mechanisms have in the development of complex immune-mediated conditions.</jats:sec
Turkish Society for Rheumatology (Turkish Takayasu Arteritis Study Group) recommendations for the diagnosis, follow-up and the treatment of Takayasu's arteritis
No full textOBJECTIVES: To develop evidence-based and expert opinion guided recommendations for Takayasu's arteritis (TAK) management. METHODS: A systematic literature review was conducted following the principles outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. To structure the key clinical questions, the task force employed the Population, Intervention, Comparison, and Outcome (PICO) format. The European League Against Rheumatism (EULAR) standardised operating procedures was subsequently applied to grade the quality of the collected evidence and determine the strength of each recommendation. RESULTS: This guideline provides 40 recommendations under the headings: diagnosis, follow-up, medical treatment, pregnancy and surgical interventions. As randomised controlled trials are very limited in number without conclusive results, most data come from case series with low-level evidence. We recommend conventional immunosuppressives as the first choice during remission-induction. Tumour necrosis factor-inhibitors or tocilizumab can be considered in patients with relapsing or refractory disease despite conventional immunosuppressives. CONCLUSIONS: The first Turkish Takayasu Arteritis Study Group recommendations deriving from a current literature review and large clinical experience, aim to guide clinicians not only in Turkey, but also in other countries who are providing health care to patients with TAK
Genetic susceptibility and validation of angiographic patterns in Takayasu arteritis
No full textFor the Turkish Takayasu Arteritis Study Group and the Vasculitis Clinical Research Consortium[Background] Prior studies identified subsets of patients with Takayasu arteritis (TAK) based on angiographic patterns of disease in cohorts from India and North America. This study aimed to validate these patterns in a TAK cohort from Turkey and determine the role of genetics in arterial patterns[Methods] 421 Turkish patients with TAK underwent angiography of the aorta and branch vessels, with disease involvement characterized in 13 arterial territories. K-means cluster analysis identified angiographically-based subgroups. 282 patients with TAK from Turkey and 115 European-American patients from North America were genotyped. Approximately 6.5 million SNPs were evaluated in a meta-analysis of both cohorts. Logistic regressions identified genetic associations with angiographic clusters (threshold for association: p-value<1x10−5). Associated variants were functionally annotated.[Results] Three clusters were identified in Turkish patients, validating the previously-identified cluster pattern. Genome-wide meta-analyses revealed a locus in the solute carrier family gene SLC24A2 in Cluster One as the most significant association (rs2891138, OR = 3.34, p-value = 2.32x10−7). Several genetic loci were associated with Cluster Two, including in LGALSL (rs883021, OR = 0.43, p-value = 1.00X10−5), AK4P3 (rs1072778, OR = 0.39, p-value = 4.07X10−6), and TMEM132B (rs4765045, OR = 3.05, p-value = 6.18X10−6). The most significant locus associated with Cluster Three was in FRMD6 (rs55692665, OR = 2.79, p-value = 1.11X10−7). Genetic effects were consistent between the cohorts. Several loci were associated with levels of mRNA expression in arterial tissues. A Cluster Two-associated variant in APBB2 (rs2465578, OR = 0.35, p-value = 6.69x10−6) showed evidence for chromatin interaction with the NSUN7 promoter and increased aortic NSUN7 expression.[Conclusions] Genetic factors are associated with distinct subsets of TAK defined by angiographic pattern of disease.NonePeer reviewe
Pregnancy Outcome in Patients with Takayasu Arteritis: The Results of Turkish Takayasu Study Group
No full textPregnancy Outcome in Patients with Takayasu Arteritis: the Results of Turkish Takayasu Study Group
No full textALIBAZ-ONER, FATMA/0000-0002-6653-1758; Yazici, Ayten/0000-0003-2167-4509[No abstract available
Pregnancy Outcome in Patients with Takayasu Arteritis: The Results of Turkish Takayasu Study Group
No full textPDCD1 polymorphisms are not associated with Takayasu's arteritis in Turkey
No full textObjectives. Takayasu's arteritis (TA) is a chronic arterial inflammation of unknown etiology involving mainly the aorta and its major branches. Based on the associations of programmed death-1 (PD-1) protein encoding gene (PDCD1) with connective tissue diseases and vasculitides, PDCD1 polymorphisms are studied for susceptibility to TA in this study. Methods. The study group is made up of TA patients (n=229) fulfilling the 1990 ACR classification criteria and compared to 193 healthy controls (HC). PD-1.3, PD-1.5 and PD-1.6 single nucleotide polymorphisms of PDCD1 gene are genotyped by polymerase chain reaction and restriction analysis (PCR-RFLP). Results. The distribution of PD-1.5 polymorphism in TA patients and HC revealed a similar presence of TT genotype in patients and controls (13.3% vs. 11.4%). PD-1.3 and PD-1.6 were less polymorphic and did not differ between the groups. Rare AA genotype of PD-1.3 (1.4% vs. 1.0%) and AG genotype of PD-1.6 was again similarly (22.4% vs. 19.2%) present in TA and HC. Conclusion. PD-1.3, 1.5 and 1.6 polymorphisms of PDCD1 gene, which were shown to be associated with various autoimmune disorders and vasculitides, are not associated with a susceptibility to TA in Turkish population
Pregnancy outcome in patients with Takayasu arteritis: the results of Turkish Takayasu Study Group.
No full text
