Defining teh Spectrum of Spondyloarthritis in Family Members of Patients w/AS

University Of Texas Hlth Sci Ctr Houston, Houston TX

Investigators

Linked publications & trials

Abstract

Ankylosing spondylitis (AS),the most common defined subgroup of diseases known as spondyloarthritis[unreadable] (SpA), includes a spectrum of disease characterized by a seronegative axial and/or peripheral arthritis with[unreadable] familial clustering, overlapping mucocutaneous and visceral features, and associations with genes in the[unreadable] major histocompatibility complex (MHC), including HLA-B27. Many seemingly distinct but inter-related[unreadable] diseases in this group include AS, acute anterior uveitis (AAU), inflammatory bowel disease (IBD) and[unreadable] psoriatic arthritis (PsA), reactive arthritis (ReA), and undifferentiated spondyloarthritis (uSpA). A large[unreadable] number of studies have defined familial aggregation in AS and other SpA, however the findings are often[unreadable] contradictory and lacking in any consistent genetic predisposing factors, due in part to biases in clinical[unreadable] ascertainment or to power concerns due to small numbers of patients or pedigrees. There is a recent[unreadable] growing trend to consider that SpA per se may be caused by specific genetic factors with which other genes[unreadable] interact to cause the development of specific phenotypes (i.e. uveitis, IBD or psoriasis). Defining these[unreadable] factors would be valuable in not only in providing clues to the pathogenesis of SpA itself and in specific[unreadable] manifestations thereof, but also in designing generic or specific interventions that could reduce the[unreadable] morbidities associated with these manifestations. In this project, we hypothesize that there are specific[unreadable] genes that predispose to SpA, with which other genes interact to produce specific phenotypic manifestations[unreadable] (i.e. psoriasis, uveitis, IBD, etc). In order to test this hypothesis, we will (1) define the prevalence and[unreadable] patterns of well-defined phenotype expression of spondyloarthritis in the first degree relatives (FDRs) of[unreadable] patients with AS, and (2) Aim 2: define the specific genetic architecture of the heterogeneity of SpA[unreadable] phenotypes in the FDR of probands with AS by traditional genetic analysis methods and novel designs using[unreadable] systems biology approach as defined in Project 4. Dr John Davis will serve as the Principal Investigator on[unreadable] this project and Dr. Michael Weismans will serve as a Co-Principal Investigator. Drs. Davis and Weisman[unreadable] have expertise in the area of clinical research and clinical care in patients with SpA. In addition, we will[unreadable] collaborate with investigators on Projects 1 (Dr. Reveille), 2 (Dr. Weisman and Ward), and 4 (Drs. Lin and[unreadable] Xiong). Drs. Lin and Xiong have expertise in both the genetic analyses and statistical modeling to be[unreadable] performed. Study coordination will be performed by two coordinators. At UCSF, Stephanie Morgan will[unreadable] coordinate 75% of the project administrative support. In addition, a coordinator at Cedar Sinai Medical[unreadable] Center will provide 25% effort to the study. We will also have the help of Myriam Bianco at the Spondylitis[unreadable] Association of America for patient recruitment and data collection.