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Genetic Determinants of Ankylosing Spondylitis Severity

This study has been completed.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) ) Identifier:
First received: March 25, 2003
Last updated: April 20, 2017
Last verified: February 21, 2017

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.

Ankylosing Spondylitis

Study Type: Observational
Official Title: Genetic Determinants of Ankylosing Spondylitis Severity - Cross Sectional Study

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 134
Study Start Date: March 20, 2003
Detailed Description:

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Participants will:

  1. have been diagnosed with AS by the modified New York criteria
  2. have had AS for 20 years or more. The duration of AS will be dated from the time of onset of symptoms of inflammatory low back pain or restricted spinal motion
  3. be able to read English.

Potential participants will be excluded if:

  1. onset of AS was at age 16 or younger
  2. have a spondyloarthropathy other than AS
  3. are unable to provide informed consent.

Study of patients with AS for 20 years or more will provide a sample with a greater proportion of patients who will have developed the outcomes of interest. All participants will necessarily be age 37 or older. Study entry is not limited by sex or ethnic origin. English literacy is required because the functional status questionnaires used in the study have not been developed and validated in many languages other than English. In particular, the HAQ-S has been validated in only English, Dutch, and Finnish. The BASFI has been validated in English, Dutch, Finnish, Swedish, German, and French. Each of these validation studies consists of a single report. Monolingual speakers of these languages are likely to be rare in our area.

Potential participants will be recruited by physician referral and self-referral. Information about the study will be mailed to local rheumatologists and posted on the NIH website. Notices will also be sent to local chapters of the Arthritis Foundation and the Spondylitis Association of America.

Study of first-degree relatives:

Participants will be:

  1. Parent, sibling, or child (age 18 or older) of an enrolled subject.
  2. Able to provide informed consent.

Family members may by asymptomatic or have signs or symptoms of AS or a condition in the spondyloarthropathy family. There is no requirement for a minimum number of members per family to be eligible for participation.

The recruitment ceiling will be unlimited. Approximately 500 subjects will be recruited from all study sites. The target sample for the primary analyses will be 400 eligible subjects. Approximately 150 subjects will be recruited at the NIH.

  Contacts and Locations
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Please refer to this study by its identifier: NCT00056849

United States, California
Cedars Sinai Medical Center
Los Angeles, California, United States, 90048-1804
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
United States, Texas
University of Texas, Houston
Houston, Texas, United States, 77030
Sponsors and Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Principal Investigator: Michael M Ward, M.D. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  More Information

Additional Information:
Responsible Party: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Identifier: NCT00056849     History of Changes
Other Study ID Numbers: 030130
Study First Received: March 25, 2003
Last Updated: April 20, 2017

Keywords provided by National Institutes of Health Clinical Center (CC):
Ankylosing Spondylitis

Additional relevant MeSH terms:
Spondylitis, Ankylosing
Bone Diseases, Infectious
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Joint Diseases
Arthritis processed this record on April 28, 2017