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Smoking and genes as determinants of SLE and RA serverity

Institution: University of California, San Francisco
Investigator(s): Michelle Freemer, M.D.
Award Cycle: 2004 (Cycle 13) Grant #: 13KT-0133 Award: $52,662
Subject Area: Epidemiology
Award Type: New Investigator Awards

Initial Award Abstract

Two autoimmune diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (lupus), cause significant disability in affected individuals. RA, which affects 1% of the American adult population, usually begins to affect people who are between the ages of 20 and 40 years. The way RA progresses in individuals varies; many patients develop disabling pain and deformities in their joints, as well as effects on other parts of the body such as the skin and lungs. Lupus, a disease that can affect any part of the body, is usually diagnosed by the age of 45 years. Although it is less common than RA, lupus can have devastating consequences including strokes, heart attacks, or kidney damage.

Unfortunately, since the cause of these autoimmune diseases is unknown, preventive or curative treatments remain elusive. Current information indicates these diseases most likely result from a combination of exposures from the environment and the inheritance of certain genes (genetic susceptibility). Studies have shown that smokers develop RA more often than nonsmokers. There is also some information that suggests that smoking may also put individuals at higher risk of developing lupus. The goal of the current project is to determine whether people who smoke develop more severe RA or lupus than nonsmokers with these diseases. In the past, investigators have only gathered information about whether people have smoked themselves, ignoring the possible effect of being exposed to tobacco smoke from others (passive smoke exposure). This study will provide new information by including information on the impact of passive smoke exposure.

Since we know that not all smokers develop RA and lupus and, conversely, some RA and lupus patients have never smoked, we recognize that there must be other factors that affect the development and severity of RA and lupus. In this study, genes that affect the metabolism of tobacco smoke will be studied in RA and lupus patients. By assessing whether RA and lupus patients who have different forms of these genes and also smoke have more severe disease than smokers without these gene variants, the effects of genes and smoking on disease severity can be better understood.

Knowledge of the impact of smoking on the seriousness of RA and lupus will allow affected patients to modify their behavior or better understand the consequences of exposure to tobacco smoke. This study may also provide information about the causes of autoimmune disease in some patients, which may lead to better treatments as well as ways of preventing these devastating diseases.