A Polymorphism in the Gene for IGF-I

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 populationbased 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. Diabetes 50:637-642, 2001

Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India

“…Of the six IGFBPs fully characterised, IGFBP-1 is considered to be the principal hour-to-hour regulator of circulating IGF activity [14], forming the link between dietary ingestion, glucose metabolism and the IGF axis. We and others have established close links between the IGF system and the development of impaired glucose tolerance, obesity and macrovascular disease [15][16][17][18]. In a white European population, we demonstrated that such changes predict the development of worsening glucose tolerance at the 5-year follow-up [6].…”

Diabetes and the risk of prostate cancer: the role of diabetes treatment and complications

“…Our finding is consistent with a study suggesting that a polymorphism in the IGF-1 gene is associated with both low IGF-1 concentrations and an increased risk of type 2 diabetes. 23 Our study had several strengths, including a large sample size, the prospective design, the ability to assess risk associated with both diabetes treatment and some diabetic complications, and the ability to control for prior PSA testing as well as a large number of other potential confounding factors. Additionally, the observed number of prostate cancer cases was greater than the expected number for our cohort, based on the number and age distribution of this cohort and SEER rates.…”

How pleiotropic genetics of the musculoskeletal system can inform genomics and phenomics of aging

“…It also calls for methods other than analyzing the "change" phenotypes to capitalize on longitudinal biomarkers. On the other hand, while high h 2 is important for predicting power for a genetic study, it does not, however, indicate how many and how strong the individual genetic factors are since the effects of all genes are pooled together (Vaessen et al 2001). …”