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Evidence for genetic variation as a factor in maintaining health^1,2,3

¹ From the Division of Genomic Medicine, University of Sheffield School of Medicine and Biomedical Science, Sheffield, United Kingdom

ABSTRACT

For many chronic diseases, the influence of genetics is subtle and complex and does not conform to simple Mendelian patterns of inheritance as is seen with single-gene disorders. Genetic variation can influence the propensity for the initiating event, the progression to a clinical disease state, and the trajectory of disease. One example of how genetic variations may affect complex diseases is provided by the interleukin 1 family of cytokines. This cytokine family plays a key role in mediating inflammation, which is a central component of many chronic diseases, including coronary artery disease and rheumatoid arthritis. Recent research has identified many sequence variations in the regulatory DNA of the genes coding for important members of the interleukin 1 family, and these variations are associated with differential effects on the inflammatory response. These in turn alter the risk of some diseases in which inflammation plays a role and also affect physiologic responses, such as the inflammatory response to exercise. As this new genetic knowledge is developed and extended, it may be possible to make health care interventions at an earlier stage, before clinical disease is established, rather than after tissues have been permanently damaged.

Key Words: Inflammation • interleukin 1 • cytokines • genetic variation • single-nucleotide polymorphism • haplotype • cardiovascular disease • rheumatoid arthritis • ankylosing spondylitis • inflammatory response to exercise

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