A polymorphism in the IGF-I gene influences the age-related decline in circulating total IGF-I levels

Eur J Endocrinol. 2003 Feb;148(2):171-5. doi: 10.1530/eje.0.1480171.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / blood*
  • Alleles
  • Heterozygote
  • Homozygote
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor I / metabolism*
  • Middle Aged
  • Polymorphism, Genetic / physiology*
  • Reference Values

Substances

  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I