title: Genetic variation in the type 2 insulin-like growth factor receptor gene and disparity in childhood height.
abstract: OBJECTIVE
  The type 2 insulin-like growth factor receptor (IGF2R) is thought to regulate insulin-like growth factor-II (IGF-II) bioavailability by degrading it in the lysosomes after uptake. We hypothesised that polymorphisms in the IGF2R gene could alter size at birth and childhood growth.
  
  
  METHODS
  The hypothesis was tested in a normal birth cohort (Avon Longitudinal Study of Parents and Children) by genotyping the IGF2R gene gly1619arg polymorphism, which causes a non-conservative amino acid change in the IGF-II binding region, using PCR and restriction fragment length polymorphism analysis.
  
  
  RESULTS
  The IGF2R gly1619arg genotype was not associated with any measure of size at birth, but A/A homozygotes grew more slowly, as determined by their change in height standard deviation scores (SDS) over the first three years (-0.70 (0.72); n = 12), than G/G homozygotes (0.00 (1.09); n = 561) (p = 0.03). They remained shorter during childhood and by the age of 7 years respective height SDS were: 0.73 (1.02) (n = 12) and 0.01 (0.99) (n = 634) (p = 0.01). These height differences persisted after adjusting for parental heights and gender. There were no detectable differences in weights at 7 years.
  
  
  CONCLUSIONS
  Allelic variation in the gly1619arg SNP of the IGF2R gene is associated with disparity in childhood stature which could reflect altered binding of IGF-II to its receptor.
authors.affiliation: Department of Paediatrics, University of Cambridge, Box 116, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Petry
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong
authors.forename: Dianne L
authors.initials: DL
authors.lastname: Wingate
authors.forename: James
authors.initials: J
authors.lastname: Brown
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Scott
authors.forename: E Yvonne
authors.initials: EY
authors.lastname: Jones
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Pembrey
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D000483:Alleles; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D011485:Protein Binding; D017527:Receptor, IGF Type 2 / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
chemical_list: D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II