Genetic Determinants of Ankylosing Spondylitis Severity

Overview

This study will explore how genes-units of heredity-may influence the severity of ankylosing spondylitis. It will examine whether some genes may cause people with ankylosing spondylitis to have more rapid fusion of the bones of the spine, more difficulty performing daily activities, or be more likely to need joint surgery. Patients who developed ankylosing spondylitis after age 16 and have had the disease for 20 years or more may be eligible for this study. The onset of disease is dated to the first appearance of symptoms of inflammatory low back pain or restricted spinal motion. Patients with a spondyloarthropathy other than AS may not enroll. Participants will complete a brief medical history and physical exam. They will fill out a 30-minute questionnaire that includes questions on demographics (such as age, ethnicity, marital status, etc.), medication history, work history, hip surgeries, and assessment of functional disability. Fifty milliliters (about 3-1/3 tablespoons) of blood will be drawn for gene testing, and X-rays will be taken of the pelvis, lower back, and neck, if recent X-rays (within 1 year) are not available. Women of childbearing age will have a urine pregnancy test before having X-rays.

The susceptibility to ankylosing spondylitis (AS) is largely genetically determined. Recent studies suggest that the severity of AS is also influenced to a large extent by genetic factors. The goal of this study is to identify genes that influence the severity of AS. We hypothesize that genetic markers of susceptibility, including human leukocyte antigen (HLA) polymorphisms, are among the genes that also influence the severity of AS. Other genes that could potentially influence the severity of AS include those that affect the severity of joint inflammation and those that influence bone formation. In this cross-sectional study, we will test the association of HLA markers and polymorphisms in several genes involved in the regulation of inflammation and bone formation with the severity of AS. Approximately 500 patients will be enrolled. Each patient will have had AS for at least 20 years. Measures of AS severity will be the extent of spinal fusion as measured radiographically, functional disability, time to permanent work disability, and need for total hip arthroplasty. Identifying genetic markers that are associated with differences in the severity of AS will greatly enhance our understanding of the pathogenesis of this disease by suggesting mechanisms and pathways involved in the development of long-term damage. In a separate but related protocol, we will assess genetic markers associated with persistent active inflammation in patients with AS.