Asthma in the workplace and related conditions, third edition. Bernstein IL, Chan-Yeun M, Malo JL, Bernstein DI, eds. New York: Taylor and Francis Group, 2006 Jan; :87-108
Common diseases such as asthma and diabetes mellitus tend to cluster in families. The risk of developing the disease if a first-degree relative is affected is 5% to 10% greater than the prevalence of the disease in the population, but less than the 25% risk for a recessive and 50% risk for a dominant single gene disorder. The familial clustering is due not to a single gene defect, but is the outcome of multiple genes (polygenic) and their interaction with the environment. Genetic variation between individuals, such as differences in blood groups, occurs frequently in the population. Such variants, whose frequency is stable between generations, are known as "polymorphisms." Polymorphisms are the basis of diversity within human populations and contribute not only to differences in characteristics such as height and blood pressure but also to variation in the ability to resist infection and handle environmental challenges. Such challenges include the response to agents inhaled at work, both inorganic and organic. Differences between individuals in their responses are likely to be determined, at least in part, by the functional consequences of polymorphisms of relevant genes, and their interactions with each other. Molecular genetic studies have provided the opportunity to identify the relevant genetic polymorphisms. However, it is important to appreciate that in a multifactorial disease such as occupational asthma (OA), a single polymorphism, although increasing susceptibility to the development of asthma in those exposed to a particular agent, is unlikely to be sufficient alone, and may even not be necessary, to cause the disease. Polymorphic genes may increase susceptibility or resistance to disease but do not determine it. The identification of a single polymorphic gene alone is therefore unlikely to provide the basis for a screening test for susceptibility to OA. Knowledge of the genes involved, the function of their protein products, and of their interaction with the relevant environmental influences does however have the potential to illuminate disease mechanisms at the molecular level and provide new opportunities to treat and prevent it.
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