A polymorphism in the IGF-I gene influences the age-related decline in circulating total IGF-I levels
OBJECTIVE: Recent studies have demonstrated an association between a 192 bp polymorphism of the IGF-I gene and total IGF-I serum levels, birth weight, body height and the risk of developing diabetes and cardiovascular diseases later on in life. This IGF-I gene polymorphism in the promoter region of the IGF-I gene may directly influence the expression of IGF-I. In the present study we evaluated the role of this polymorphism in the age-related decline in serum IGF-I levels. SUBJECTS AND METHODS: All subjects were participants of the Rotterdam Study, a population-based cohort study of diseases in the elderly. We studied a total group of 346 subjects, who comprised two subgroups: a randomly selected population-based sample of 196 subjects, and a group of 150 subjects selected on IGF-I genotype. In the total group of 346 individuals the relationship between this 192 bp polymorphism and the age-related decline in circulating total IGF-I levels was studied. RESULTS: Homozygous carriers of the 192 bp allele demonstrated significant decline in serum IGF-I with age (r=-0.29, P=0.002). This decline is similar to that seen in the general population. An age-related decline in serum total IGF-I was not observed in heterozygotes (r=-0.06, P=0.48) and non-carriers (r = -0.12, P=0.32). Interestingly, the relationship between age and serum IGF-binding protein-3 levels showed the same pattern. CONCLUSION: We observed only in homozygous carriers of the 192 bp alleles of the IGF-I gene an age-related decline in circulating total IGF-I levels, but not in heterozygotes and non-carriers of the 192 bp allele. We hypothesize that this IGF-I gene polymorphism directly or indirectly influences GH-mediated regulation of IGF-I secretion.
|Keywords||0 (Insulin-Like Growth Factor Binding Protein 3), 67763-96-6 (Insulin-Like Growth Factor I), Aged, Aging/*blood, Alleles, Diabetes and related disorders, Heterozygote, Homozygote, Human, Insulin-Like Growth Factor Binding Protein 3/blood, Insulin-Like Growth Factor I/*genetics/*metabolism, Middle Aged, Polymorphism (Genetics)/*physiology, Reference Values, Support, Non-U.S. Gov't|
|Persistent URL||dx.doi.org/10.1530/eje.0.1480171, hdl.handle.net/1765/5937|
Rietveld, I., Janssen, J.A.M.J.L., Hofman, A., van Duijn, C.M., Lamberts, S.W.J., & Pols, H.A.P.. (2003). A polymorphism in the IGF-I gene influences the age-related decline in circulating total IGF-I levels. European Journal of Endocrinology, 148(2), 171–175. doi:10.1530/eje.0.1480171