A polymorphism in the gene for IGF-I - Functional properties and risk for type 2 diabetes and myocardial infarction

Evidence is accumulating that low levels of IGF-I play a role in the pathog enesis 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 rela tion to circulating IGF-I levels and growth measured as body height, and we studied the relationship of this polymorphism with type 2 diabetes and myo cardial infarction, The relation between the IGF-I polymorphism and body he ight was assessed in a population-based sample of 900 subjects from the Rot terdam Study. Within each genotype stratum, 50 subjects were randomly selec ted for a study of the relation of this polymorphism with serum IGF-I level s, To assess the risk for type 2 diabetes, we studied 220 patients and 596 normoglycemic control subjects. For myocardial infarction, 477 patients wit h evidence of myocardial infarction on electrocardiogram and 808 control su bjects 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 o riginated. Body height was, con average, 2.7 cm lower (95% CI for differenc e -4.6 to -0.8 cm, P = 0.004), and serum IGF-I concentrations were 18% lowe r (95% CI for difference -6.0 to -1.3 mmol/l, P = 0.003) in subjects who di d not carry the 192-bp allele, In noncarriers of the 192-bp allele, an incr eased relative risk for type 2 diabetes (1.7 [95% CI 1.1-2.7]) and for myoc ardial 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 gene tically determined exposure to relatively low IGF-I levels is associated wi th an increased risk for type 2 diabetes and myocardial infarction.