Evidence is accumulating that low levels of IGF-I play a role in the pathogenesis of type 2 diabetes and cardiovascular diseases. We examined the role of a genetic polymorphism in the promoter region of the IGF-I gene in relation to circulating IGF-I levels and growth measured as body height, and we studied the relationship of this polymorphism with type 2 diabetes and myocardial infarction. The relation between the IGF-I polymorphism and body height was assessed in a population-based sample of 900 subjects from the Rotterdam Study. Within each genotype stratum, 50 subjects were randomly selected for a study of the relation of this polymorphism with serum IGF-I levels. To assess the risk for type 2 diabetes, we studied 220 patients and 596 normoglycemic control subjects. For myocardial infarction, 477 patients with evidence of myocardial infarction on electrocardiogram and 808 control subjects were studied. A 192-bp allele was present in 88% of the population, suggesting that this is the wild-type allele from which all other alleles originated. Body height was, on average, 2.7 cm lower (95% CI for difference -4.6 to -0.8 cm, P = 0.004), and serum IGF-I concentrations were 18% lower (95% CI for difference -6.0 to -1.3 mmol/l, P = 0.003) in subjects who did not carry the 192-bp allele. In noncarriers of the 192-bp allele, an increased relative risk for type 2 diabetes (1.7 [95% CI 1.1-2.7]) and for myocardial infarction (1.7 [95% CI 1.1-2.5]) was found. In patients with type 2 diabetes, the relative risk for myocardial infarction in subjects without the 192-bp allele was 3.4 (95% CI 1.1-11.3). Our study suggests that a genetically determined exposure to relatively low IGF-I levels is associated with an increased risk for type 2 diabetes and myocardial infarction.

Additional Metadata
Keywords *Genetic Predisposition to Disease, *Polymorphism, Genetic/physiology, Aged, Alleles, Body Height, Diabetes Mellitus, Type 2/blood/*genetics, Female, Humans, Insulin-Like Growth Factor I/analysis/*genetics/physiology, Male, Middle aged, Myocardial Infarction/blood/*genetics, Promoter Regions (Genetics)/genetics, Reference Values, Research Support, Non-U.S. Gov't
Persistent URL hdl.handle.net/1765/9610
Citation
Vaessen, N., Witteman, J.C.M., Testers, L., Lamberts, S.W.J., Oostra, B.A., Pols, H.A.P., … Hofman, A.. (2001). A polymorphism in the gene for IGF-I: functional properties and risk for type 2 diabetes and myocardial infarction. Diabetes. Retrieved from http://hdl.handle.net/1765/9610