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

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.

• Authors: Ingrid Rietveld, Joop A M J L Janssen, Albert Hofman, Huibert A P Pols, Cornelia M van Duijn, Steven W J Lamberts
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 148 Issue 2 Pg. 171-5 (Feb 2003) ISSN: 0804-4643 [Print] England
• PMID: 12590635 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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