Analyzing the Association of Gene Variants With Increased Risk of Coronary Heart Disease in Women With Systemic Lupus Erythematosus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00563082
Recruitment Status : Completed
First Posted : November 26, 2007
Last Update Posted : March 21, 2014
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of Pittsburgh

Brief Summary:
Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects younger premenopausal women. The risk of coronary heat disease (CHD) in women with SLE is up to 50 times higher than in the general population. The conventional risk factors are insufficient to explain this increased risk of CHD in SLE-affected women. This study will perform genetic analysis to determine if genetic variation in the F2 gene is associated with both SLE risk and CHD risk in women with SLE.

Condition or disease
Lupus Erythematosus, Systemic

Detailed Description:

SLE is a condition of chronic inflammation of the internal organs, caused by an autoimmune disease. An autoimmune disease is a disorder in which the body's immune system attacks its own tissues through production of abnormal antibodies in the blood. Current treatments for SLE focus on reducing inflammation and production of unusual antibodies. While the exact cause of SLE is unknown, genetics, drugs, viruses, and ultraviolent light are all possible contributors. Previous genetic studies have determined that antiphospholipid antibodies (APA) are present in 50% of people with SLE compared with only 1 to 5% in the general U.S. white population. These antibodies interfere with standard blood vessel function, resulting in blood clots and narrowing of vessels. The F2 gene codes for prothrombin, a precursor of thrombin, which is a key enzyme in blood clotting. Prothrombin can be detected by APA as an antigen, resulting in anti-F2 antibodies. Recent studies have reported the association of F2 genetic variants with non-fatal heart attack, further suggesting that the F2 gene and APA play a role in CHD. In addition to being a biological candidate gene for CHD, F2 is also a positional candidate gene for SLE, as it is close to a region of linkage for SLE on chromosome 11. This study will perform genetic analysis to determine if genetic variation in the F2 gene is associated with both SLE risk and CHD risk in women with SLE.

Using genetic analysis techniques, this study will examine previously collected case-control samples of serum DNA. Study researchers will resequence the entire F2 gene and then examine the role of sequence variations in relation to SLE and the risk of CHD in SLE patients. Researchers will identify rare and common variants of the F2 gene and further screen variants to determine gene-trait relations.

Study Type : Observational
Actual Enrollment : 1254 participants
Observational Model: Case Control
Time Perspective: Retrospective
Official Title: Prothrombin Gene Varitaion and Risk of SLE and CHD
Study Start Date : May 2000
Actual Study Completion Date : August 2007

Resource links provided by the National Library of Medicine

SLE participants positive for both APA and CHD
Normal participants with a high titer of APA

Primary Outcome Measures :
  1. Rare and common variants of F2 that contribute to SLE risk and CHD risk in SLE [ Time Frame: Measured at Year 4 ]

Biospecimen Retention:   Samples With DNA
DNA and serum

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
The study population will include genetic samples from women with SLE and CHD and from normal control women. The population will be 80.5% U.S. white women and 19.5% U.S. black women.

Inclusion Criteria:

  • Diagnosis of SLE

Exclusion Criteria:

  • Pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00563082

Sponsors and Collaborators
University of Pittsburgh
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: M. Ilyas Kamboh, PhD University of Pittsburgh

Responsible Party: University of Pittsburgh Identifier: NCT00563082     History of Changes
Other Study ID Numbers: 1393
R01HL088648 ( U.S. NIH Grant/Contract )
R01HL088648-01 ( U.S. NIH Grant/Contract )
First Posted: November 26, 2007    Key Record Dates
Last Update Posted: March 21, 2014
Last Verified: March 2014

Keywords provided by University of Pittsburgh:

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases