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Diabetes 50:637-642, 2001
© 2001 by the American Diabetes Association, Inc.

A Polymorphism in the Gene for IGF-I

Functional Properties and Risk for Type 2 Diabetes and Myocardial Infarction

Norbert Vaessen1,2, Peter Heutink2, Joop A. Janssen3, Jacqueline C. M. Witteman1, Leon Testers1, Albert Hofman1, Steven W. J. Lamberts3, Ben A. Oostra2, Huibert A. P. Pols1,3, and Cornelia M. van Duijn1

1 Department of Epidemiology and Biostatistics, the
2 Center for Biomedical Genetics, Department of Clinical Genetics, and the
3 Department of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands

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.

Abbreviations: ECG, electrocardiogram; PCR, polymerase chain reaction; WHR, waist-to-hip ratio


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