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JACI Highlights - March 2009Roles of arginase variants, atopy and ozone in childhood asthmaMuhammad T. Salam, MS, MD, Talat Islam, MBBS, PhD, W. James Gauderman, PhD, Frank D Gilliland, MD PhD It’s well documented that genetic and environmental factors have an influence on the risk for asthma. Researchers have been trying to determine which genes are active in the asthma disease process. There is increasing evidence for a role of arginase, a liver enzyme, in the origins of asthma. It has been proposed that a variation in arginase genes may contribute to asthma and atopy in children, although studies in humans are limited. A recent study has implicated the variants arginase I (ARG1) and arginase II (ARG2) in asthma. This study, led by Muhammad Salam and published in the March 2009 issue of The Journal of Allergy and Clinical Immunology, found that genetic (atopy) and environmental (ozone) factors influenced the asthma risk associated with ARG1 but not with ARG2 variants. This is a new finding that suggests that atopy and ozone could influence the expression of these two genes differently. In theory, control of arginase activity in the lung may be a useful approach to the prevention and treatment of asthma. The authors found that the effect of ARG1 on asthma may be modulated by atopy (Th2-type cytokines) and exposure to ozone. The normal function of arginase is to convert L-arginine to L-ornithine, leading to cell proliferation and collagen synthesis which could lead to airway remodeling. Airway remodeling is a pathological feature of asthma involving goblet cell hyperplasia, airway smooth muscle hypertrophy and fibrosis. That’s why the expression of arginase in the lung has been a focus in experimental asthma, specifically regarding remodeling and airway hyper-responsiveness. Further research is needed to identify novel variants and determine their impact on arginase activity, airway inflammation and airways hyper-responsiveness. This could explain the possible mechanism(s) by which variants in these genes could affect asthma risk in children.
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