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University of Pittsburgh Schools of the Health Sciences

University Of Pittsburgh Receives $1.8 Million NIH Grant For Genetic Study Of Heart Disease Risk In Women With Lupus

PITTSBURGH, January 8, 2003 Researchers at the University of Pittsburgh Graduate School of Public Health (GSPH) have received a grant of $1.8 million from the National Institutes of Health (NIH) for a five-year study of how genetic variations contribute to the risk of coronary heart disease (CHD) in women with systemic lupus erythematosus.

Systemic lupus erythematosus is a prototypic systemic inflammatory autoimmune disease that affects mainly premenopausal women. It is three to four times more prevalent among African-Americans than among whites. The risk of CHD in women with lupus is up to 50 times higher than in the general population.

The newly funded study will examine how genetic variations modify the risk of CHD among women with lupus.

Antiphospholipid antibodies (APA) are found in half of all women with lupus, compared with only 1 percent to 5 percent of the general population.

APA are produced mainly against the apolipoprotein H (apoH) protein in people with autoimmune diseases such as lupus. Under normal circumstances, apoH inhibits the uptake of oxidized low-density lipoprotein (LDL) cholesterol (known as bad cholesterol) by cells in blood vessels. Conversely, in the presence of APA, apoH promotes the absorption of LDL.

As the accumulation of oxidized LDL cholesterol is believed to initiate the atherosclerotic process, we believe that apoH-mediated immune response in patients with autoimmune diseases like lupus may lead to atherosclerosis, said principal investigator M. Ilyas Kamboh, Ph.D., professor of human genetics at GSPH. This study will determine whether individuals who are positive for APA and/or for antibodies to oxidize LDL cholesterol are prone to premature coronary heart disease and whether this susceptibility is modified by common genetic variation in the apoH gene.

The study will be conducted in collaboration with Susan Manzi, M.D., co-director of the University of Pittsburghs Lupus Diagnostic and Treatment Center.

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