A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analysed in 2,134 cases and 9,125 unaffected controls from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, P = 1.94E-54, per-allele OR = 1.79; and rs9275592, P = 1.14E-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, P = 1.23E-10, OR = 1.28; and rs128738, P = 4.60E-09, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Cross-national health care database utilization between Spain and France: results from the EPICHRONIC study assessing the prevalence of type 2 diabetes mellitus

Guillaume Moulis,1–3,* Berta Ibañez,4–6,* Aurore Palmaro,2,3 Felipe Aizpuru,6–8 Eduardo Millan,6,8 Maryse Lapeyre-Mestre,2,3,9 Laurent Sailler,1–3 Koldo Cambra5,6,10 1Department of Internal Medicine, Toulouse University Hospital, Toulouse, France; 2UMR1027 INSERM, University of Toulouse, Toulouse, France; 3Clinical Investigation Center 1436, Toulouse University Hospital, Toulouse, France; 4Navarrabiomed, Health Department, Public University of Navarra, Pamplona, Spain; 5IdiSNA, Pamplona, Spain; 6Health Service Research on Chronic Patients Network (REDISSEC), Pamplona, Spain; 7Research Unit Araba (BioAraba), Osakidetza-Basque Health Department, Vitoria-Gasteiz, Spain; 8Healthcare Services Sub-directorate, Osakidetza-Basque Health Service, Araba, Spain; 9Department of Medical and Clinical Pharmacology, Toulouse University Hospital, Toulouse, France; 10Institute of Public Health and Labour Health of Navarra, Pamplona, Spain *These authors contributed equally to this work Aim: The EPICHRONIC (EPIdemiology of CHRONIC diseases) project investigated the possibility of developing common procedures for French and Spanish electronic health care databases to enable large-scale pharmacoepidemiological studies on chronic diseases. A feasibility study assessed the prevalence of type 2 diabetes mellitus (T2DM) in Navarre and the Basque Country (Spain) and the Midi-Pyrénées region (France). Patients and methods: We described and compared database structures and the availability of hospital, outpatient, and drug-dispensing data from 5.9 million inhabitants. Due to differences in database structures and recorded data, we could not develop a common procedure to estimate T2DM prevalence, but identified an algorithm specific to each database. Patients were identified using primary care diagnosis codes previously validated in Spanish databases and a combination of primary care diagnosis codes, hospital diagnosis codes, and data on exposure to oral antidiabetic drugs from the French database. Results: Spanish and French databases (the latter termed Système National d’Information Inter-Régimes de l’Assurance Maladie [SNIIRAM]) included demographic, primary care diagnoses, hospital diagnoses, and outpatient drug-dispensing data. Diagnoses were encoded using the International Classification of Primary Care (version 2) and the International Classification of Diseases, version 9 and version 10 (ICD-9 and ICD-10) in the Spanish databases, whereas the SNIIRAM contained ICD-10 codes. All data were anonymized before transferring to researchers. T2DM prevalence in the population over 20 years was estimated to be 6.6–7.0% in the Spanish regions and 6.3% in the Midi-Pyrénées region with ~2% higher estimates for males in the three regions. Conclusion: Tailored procedures can be designed to estimate the prevalence of T2DM in population-based studies from Spanish and French electronic health care records. Keywords: epidemiology, pharmacoepidemiology, electronic health care database, cross-national study, population-based study, type 2 diabetes mellitu

Increased ischemic stroke, acute coronary artery disease and mortality in patients with granulomatosis with polyangiitis and microscopic polyangiitis

International audienceObjective: The aim of our study was to assess major cardiovascular event incidence, predictors, and mortality in ANCA-associated vasculitis (AAV).Methods: We conducted a retrospective cohort study of all GPA or MPA, according to Chapel Hill Consensus Conference classification criteria, diagnosed between 1981 and 2015. Major cardiovascular event was defined as acute coronary artery disease, or ischemic stroke, or peripheral vascular disease requiring a revascularization procedure. We calculated the comparative morbidity/mortality figure (CMF) and we used Cox proportional hazards regression models to assess the risk of coronary artery disease, ischemic stroke associated with AAV, after adjusting for covariates.Results: 125 patients, 99 GPA (79,2%) and 26 MPA (20,8%), were followed 88.4 ± 78.3 months. Ischemic stroke incidence was four times higher than in the general population (CMF 4,65; 95% CI 4,06-5,31). Coronary artery disease incidence was four times higher than in the general population (CMF 4,22; 95% CI 1,52-11,68). Smoking habits and history of coronary artery disease were strongly associated with coronary artery disease occurrence (adjusted HR 8.8; 95% CI 2.12-36.56, and adjusted HR 10.3; 95% CI 1.02-104.5, respectively). ENT flare-up was an independent protective factor for coronary artery disease occurrence. We did not identify factors significantly associated with stroke occurrence. The age-adjusted mortality rate was 22.5 per 1000 person-years. Mortality in AAV was 1.5 times higher than in the general population (CMF 1.56; 95% CI 1.34-1.83).Conclusion: AAV have a significantly increased risk of mortality, ischemic stroke, and coronary artery disease