Genetics of the neuronal NO synthase (NOS1) in the etiology of bronchial asthma

Abstract

The free radical nitric oxide (NO) is endogenously produced by enzymes known as NO synthases. NO in the airways is involved in a number of pathophysiological processes, such as airway inflammation, allergic reactions, and asthma. Asthma is a multifactorial disease that is caused by environmental and genetic factors. Genome wide screening approaches in families revealed evidence for linkage between chromosomal region 12q and allergic diseases, increased serum IgE levels as well as the development of asthma. The gene encoding for neuronal NOS (NOS1) is an attractive candidate gene for asthma, not only because it is localized in chromosomal region 12q24. Experimental studies in animals and humans suggest that NOS1 plays an important role in asthma. For instance, in a murine model of allergic asthma, NOS1 has been shown to be important for the development of bronchial hyperresponsiveness, since mice deficient for the nos1 gene were less responsive to airway challenge than both wild-type mice and mice deficient for the nos2 gene. Case-control studies in humans revealed allelic associations between polymorphic markers in the NOS1 gene and the diagnosis of asthma. Furthermore, increased concentrations of NO in the airways of asthmatics are closely related to the size of an intronic (AAT)(n)-repeat polymorphism in the NOS1 gene. The purpose of this review is to summarize studies that provide evidence for an involvement of NOS1 in the genetics of asthma.