title: Insulin-like growth factor I gene promoter polymorphism, collagen type II alpha1 (COL2A1) gene, and the prevalence of radiographic osteoarthritis: the Rotterdam Study.
abstract: OBJECTIVE
  To examine the role of an IGF-I gene promoter polymorphism in the prevalence of radiographic osteoarthritis (ROA), and study its interaction with the COL2A1 gene.
  
  
  METHODS
  Individuals genotyped for IGF-I (n = 1546) and COL2A1 gene polymorphisms (n = 808) were selected from a random sample (n = 1583) derived from the Rotterdam study. The presence of ROA was defined as a Kellgren score of 2 or more in at least one of four joints (knee, hip, hand, and spine). Genotype specific odds ratios (OR) were adjusted for age, sex, body mass index, and bone mineral density using logistic regression. Interaction with the COL2A1 genotype was tested.
  
  
  RESULTS
  Overall, no association was found between the IGF-I polymorphism and ROA. In subjects aged 65 years or younger (n = 971), the prevalence of ROA increased with the absence of the 192 base pair (bp) allele (p for trend = 0.03). Compared with homozygotes for the 192 bp allele, the prevalence of ROA was 1.4 times higher in heterozygotes (95% confidence interval, 1.0 to 1.8) and 1.9 times higher in non-carriers (1.1 to 3.3). There was evidence of interaction between the IGF-I and COL2A1 genes. Individuals with the risk genotype of both genes had an increased prevalence of ROA (OR 3.4 (1.1 to 10.7)). No effect was observed in subjects older than 65 years.
  
  
  CONCLUSIONS
  
  
  
  METHODS
  with genetically determined low IGF-I expression (non-carriers of the 192 bp allele) may be at increased risk of ROA before the age of 65 years. Furthermore, an interaction between the IGF-I and COL2A1 genes is suggested.
authors.affiliation: Nehterlands Institute for Health Sciences, Rotterdam, Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Zhai
authors.forename: F
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: J J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.forename: I
authors.initials: I
authors.lastname: Meulenbelt
authors.forename: C
authors.initials: C
authors.lastname: Bijkerk
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: J B J
authors.initials: JB
authors.lastname: van Meurs
authors.forename: A G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: H A P
authors.initials: HA
authors.lastname: Pols
authors.forename: P E
authors.initials: PE
authors.lastname: Slagboom
authors.forename: C M
authors.initials: CM
authors.lastname: van Duijn
mesh_terms: D000368:Aged; D024043:Collagen Type II / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D011859:Radiography; D012307:Risk Factors
chemical_list: D024043:Collagen Type II; D007334:Insulin-Like Growth Factor I