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

Study Overview
=================
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.

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.

Official Title
-----------------
Prothrombin Gene Varitaion and Risk of SLE and CHD

Conditions
-----------------
Lupus Erythematosus, Systemic

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of SLE Exclusion Criteria: Pregnant

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>SLE participants positive for both APA and CHD | |
| 2<br>Normal participants with a high titer of APA | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rare and common variants of F2 that contribute to SLE risk and CHD risk in SLE |  | Measured at Year 4 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SLE, Genetics