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

Norbert Vaessen, Peter Heutink, Joop A. Jansen, Jacqueline C.M. Witteman, Leon Testers, Albert Hofman, Steven W.J. Lamberts, Ben A. Oostra, Huib A. Pols*, Cornelia M. van Duijn

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)637-642
Number of pages6
JournalDiabetes
Volume50
Issue number3
DOIs
Publication statusPublished - Mar 2001

Research programs

  • EMC 02-01-38-01-01
  • EMC 02-01-38-02-00
  • EMC MGC-02-96-01
  • EMC NIHES-01-64-02

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