Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA.
BACKGROUND
A polymorphism in the human GH receptor gene (d3/fl-GHR) resulting in genomic deletion of exon 3 has been associated with the degree of height increase in response to GH therapy.


OBJECTIVE
The objective of the study was to evaluate the frequencies of d3/fl-GHR polymorphism genotypes in control and short small-for-gestational-age (SGA) populations.


METHODS
An adult control population with heights normally distributed (ACPNH) between -2 and +2 sd score (SDS) and a short non-GH-deficient SGA child population were selected.


METHODS
Thirty Spanish hospitals participated in the selection of the short non-GH-deficient SGA children in the setting of a controlled, randomized trial, and one of these hospitals selected the ACPNH. CONTROLS AND PATIENTS: Two hundred eighty-nine adult subjects of both sexes constituted the ACPNH and 247 children and adolescents of both sexes the short SGA patients.


METHODS
Heights and weights were recorded in the ACPNH, and auxologic and biochemical data were recorded at each hospital for the SGA patients; d3/fl-GHR genotypes were determined and data analyzed in a single hospital.


RESULTS
In short SGA patients, d3/fl-GHR genotype frequencies were significantly different from those in ACPNH, with a higher frequency of fl/fl genotype (P < 0.0001). In ACPNH, a trend toward diminished d3/d3 genotype frequency was observed in the shortest height group (height <or=-1 SDS and >or=-2 SDS, n = 60).


CONCLUSIONS
Our data showed significant differences in the frequency distribution of the d3/fl-GHR genotypes between a normally distributed adult height population and short SGA children, with the biologically less active fl/fl genotype being almost twice as frequent in SGA patients. These data suggest that the d3/fl-GHR polymorphism might be considered among the factors that contribute to the phenotypic expression of growth.
Audí
Laura
L
Department of Pediatrics, Hospital Vall D'Hebron, Autonmous University, Barcelona, Spain. laudi@ir.vhebron.net
Esteban
Cristina
C
Carrascosa
Antonio
A
Espadero
Rosa
R
Pérez-Arroyo
Annalisa
A
Arjona
Rosa
R
Clemente
María
M
Wollmann
Hartmut
H
Fryklund
Linda
L
Parodi
Luis A
LA
D000293:Adolescent; D000328:Adult; D001827:Body Height / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D035061:Control Groups; D004393:Dwarfism, Pituitary / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011986:Receptors, Somatotropin / Q000235:genetics*
D011986:Receptors, Somatotropin