A putative functional polymorphism in the IGF-I gene: association studies with type 2 diabetes, adult height, glucose tolerance, and fetal growth in U.K. populations.
IGF-I has a critical role in growth and metabolism. A microsatellite polymorphism 1 kb upstream to the IGF-I gene has recently been associated with several adult phenotypes. In a large Dutch cohort, the absence of the commonest allele (Z) was associated with reduced serum IGF-I levels, reduced height, and an increased risk of type 2 diabetes and myocardial infarction. This result has not been replicated, and the role of this polymorphism in these traits in U.K. subjects is not known. We sought further evidence for the involvement of this variant in type 2 diabetes using a case-control study and IGF-I and diabetes-related traits in a population cohort of 640 U.K. individuals aged 25 years. Absence of the common allele was not associated with type 2 diabetes (odds ratio 0.70, 95% CI 0.47-1.04 for X/X versus Z/Z genotype, chi(2) test for trend across genotypes, P = 0.018). In the population cohort, the common allele (Z) was associated with decreased IGF-I levels (P = 0.01), contrary to the Dutch study, but not with adult height (P = 0.23), glucose tolerance (P = 0.84), oral glucose tolerance test-derived values of beta-cell function (P = 0.90), or insulin resistance (P = 0.66). There was no association with measures of fetal growth, including birth weight (P = 0.17). Our results do not support the previous associations and suggest that the promoter microsatellite is unlikely to be functionally important.
Frayling
Timothy M
TM
Department of Diabetes and Vascular Medicine, University of Exeter, Barrack Road, Exeter EX2 5AX, U.K.
Hattersley
Andrew T
AT
McCarthy
Anne
A
Holly
Jeff
J
Mitchell
Simon M S
SM
Gloyn
Anna L
AL
Owen
Katharine
K
Davies
David
D
Smith
George Davey
GD
Ben-Shlomo
Yoav
Y
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D001827:Body Height / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D011110:Polymorphism, Genetic; D006113:United Kingdom
D001786:Blood Glucose; D007334:Insulin-Like Growth Factor I