title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Rietveld
authors.forename: Joop A M J L
authors.initials: JA
authors.lastname: Janssen
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Huibert A P
authors.initials: HA
authors.lastname: Pols
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Steven W J
authors.initials: SW
authors.lastname: Lamberts
mesh_terms: D000368:Aged; D000375:Aging / Q000097:blood*; D000483:Alleles; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology*; D012016:Reference Values
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I