title: A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone.
abstract: Growth hormone is used to increase height in short children who are not deficient in growth hormone, but its efficacy varies largely across individuals. The genetic factors responsible for this variation are entirely unknown. In two cohorts of short children treated with growth hormone, we found that an isoform of the growth hormone receptor gene that lacks exon 3 (d3-GHR) was associated with 1.7 to 2 times more growth acceleration induced by growth hormone than the full-length isoform (P < 0.0001). In transfection experiments, the transduction of growth hormone signaling through d3-GHR homo- or heterodimers was approximately 30% higher than through full-length GHR homodimers (P < 0.0001). One-half of Europeans are hetero- or homozygous with respect to the allele encoding the d3-GHR isoform, which is dominant over the full-length isoform. These observations suggest that the polymorphism in exon 3 of GHR is important in growth hormone pharmacogenetics.
authors.affiliation: U561 INSERM, Saint Vincent de Paul Hospital, Paris V University, 82 Avenue Denfert-Rochereau, 75014 Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Dos Santos
authors.forename: Laurent
authors.initials: L
authors.lastname: Essioux
authors.forename: Cécile
authors.initials: C
authors.lastname: Teinturier
authors.forename: Maïté
authors.initials: M
authors.lastname: Tauber
authors.forename: Vincent
authors.initials: V
authors.lastname: Goffin
authors.forename: Pierre
authors.initials: P
authors.lastname: Bougnères
mesh_terms: D001827:Body Height; D002648:Child; D002675:Child, Preschool; D019281:Dimerization; D005091:Exons; D005260:Female; D005838:Genotype; D013006:Growth Hormone / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction
chemical_list: D011986:Receptors, Somatotropin; D013006:Growth Hormone