Analyzing the Association of Gene Variants With Increased Risk of Coronary Heart Disease in Women With Systemic Lupus Erythematosus
Condition: Lupus Erythematosus, Systemic
MeSH terms: Lupus Erythematosus, Systemic
Study type: Observational

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.
    

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.
    

Observational model: Case-Control
Time perspective: Retrospective
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.
      
Biospecimen description: 
      DNA and serum
    
Keywords: SLE; Genetics