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  • Title: Genetic variation in the type 2 insulin-like growth factor receptor gene and disparity in childhood height.
    Author: Petry CJ, Ong KK, Wingate DL, Brown J, Scott CD, Jones EY, Pembrey ME, Dunger DB, Alspac Study Team.
    Journal: Growth Horm IGF Res; 2005 Dec; 15(6):363-8. PubMed ID: 16172012.
    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. DESIGN AND 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. CONCLUSION: 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.
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