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 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.
Vaessen
N
N
Department of Epidemiology and Biostatistics, the Center for Biomedical Genetics, Rotterdam, The Netherlands.
Heutink
P
P
Janssen
J A
JA
Witteman
J C
JC
Testers
L
L
Hofman
A
A
Lamberts
S W
SW
Oostra
B A
BA
Pols
H A
HA
van Duijn
C M
CM
D000368:Aged; D000483:Alleles; D001827:Body Height; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012016:Reference Values
D007334:Insulin-Like Growth Factor I