This Project centers on the VCRC Genetics and Genomics Program and includes a broad range of individual scientific projects exploring i) the genetic basis of vasculitis in terms of disease susceptibility, clinical expression and outcome, and response to treatment;ii) the molecular pathophysiology of vasculitis;and iii) potential biomarkers useful for the management of these complex diseases. The recent history of genetics research in rare diseases makes it clear that only through collaboration and cooperation can study populations of meaningful sizes be assembled to conduct genome-wide association studies. The VCRC has established productive collaborations within the international vasculitis communities to conduct such shared genetic research, and also to conduct candidate gene studies and to perform exome sequencing to identify genes containing rare variants. Genomic DNA has been obtained from the >1700 patients already enrolled in VCRC studies, and that number will increase greatly during the next 5 years. Gene expression profiling and epigenetics provide complementary insights into the pathophysiology of disease and can also be used to identify biomarkers of important clinical outcomes. RNA already collected from two VCRC clinical trials will be analyzed for this purpose. The existing protocols for sample collection in the VCRC Longitudinal Studies can easily be adapted to collect DNA (epigenetics) and RNA (gene expression) longitudinally.
The Specific Aims of this Project are to: 1) continue to collect genomic DNA and linked comprehensive clinical data from patients with multiple forms of vasculitis to conduct large-scale collaborative genetics studies;2) conduct a series of candidate gene analyses and genome-wide association studies;3) conduct studies of exome sequencing in order to identify genes with rare variants associated with risk of vasculitis;4) study gene expression profiles from the whole blood of patients with vasculitis during active disease and remission, to identify signatures and molecular pathways related to disease activity, response to therapy, and/or long-term prognosis;and 5) study DNA methylation patterns (epigenetics) in white blood cells to gain insight into pathophysiology of vasculitis and to investigate another potential source of biomarkers useful for diagnosis or prognosis.

Public Health Relevance

The Vasculitis Clinical Research Consortium (VCRC) is an extensive infrastructure that allows experts in multiple centers to collaborate on research in vasculitis, a group of rare and serious diseases that feature inflammatory destruction of blood vessels. The VCRC provides an important contribution to international efforts to use state-of-the-art technology to determine the contributions of genetics and gene expression to the cause and course of vasculitis.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZTR1-CI-8 (01))
Program Officer
Wang, Yan Z
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University of Pennsylvania
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Hatemi, Gulen; Merkel, Peter A; Hamuryudan, Vedat et al. (2014) Outcome measures used in clinical trials for Beh├žet syndrome: a systematic review. J Rheumatol 41:599-612
Monach, Paul A (2014) Biomarkers in vasculitis. Curr Opin Rheumatol 26:24-30
Grayson, Peter C; Amudala, Naomi A; McAlear, Carol A et al. (2014) Causal attributions about disease onset and relapse in patients with systemic vasculitis. J Rheumatol 41:923-30
Merkel, Peter A; Aydin, Sibel Z; Boers, Maarten et al. (2014) Current status of outcome measure development in vasculitis. J Rheumatol 41:593-8
Mooney, Janice; Spalding, Nicola; Poland, Fiona et al. (2014) The informational needs of patients with ANCA-associated vasculitis-development of an informational needs questionnaire. Rheumatology (Oxford) 53:1414-21
Langford, Carol A; Monach, Paul A; Specks, Ulrich et al. (2014) An open-label trial of abatacept (CTLA4-IG) in non-severe relapsing granulomatosis with polyangiitis (Wegener's). Ann Rheum Dis 73:1376-9
Kermani, Tanaz A; Warrington, Kenneth J; Crowson, Cynthia S et al. (2013) Large-vessel involvement in giant cell arteritis: a population-based cohort study of the incidence-trends and prognosis. Ann Rheum Dis 72:1989-94
Monach, Paul A; Warner, Roscoe L; Tomasson, Gunnar et al. (2013) Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis. Ann Rheum Dis 72:1342-50
Schmidt, Jean; Kermani, Tanaz A; Bacani, A Kirstin et al. (2013) Diagnostic features, treatment, and outcomes of Takayasu arteritis in a US cohort of 126 patients. Mayo Clin Proc 88:822-30
Grayson, Peter C; Amudala, Naomi A; Mcalear, Carol A et al. (2013) Illness perceptions and fatigue in systemic vasculitis. Arthritis Care Res (Hoboken) 65:1835-43

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