The -202 A allele of insulin-like growth factor binding protein-3 (IGFBP3) promoter polymorphism is associated with higher IGFBP-3 serum levels and better growth response to growth hormone treatment in patients with severe growth hormone deficiency.
BACKGROUND
Genetic factors that influence the response to recombinant human GH (rhGH) therapy remain mostly unknown. To date, only the GH receptor gene has been investigated.


OBJECTIVE
The aim of the study was to assess the influence of a polymorphism in the IGF-binding protein-3 (IGFBP-3) promoter region (-202 A/C) on circulating IGFBP-3 levels and growth response to rhGH therapy in children with GH deficiency (GHD).


METHODS
-202 A/C IGFBP3 genotyping (rs2854744) was correlated with data of 71 children with severe GHD who remained prepubertal during the first year of rhGH treatment.


METHODS
We measured IGFBP-3 levels and first year growth velocity (GV) during rhGH treatment.


RESULTS
Clinical and laboratory data at the start of treatment were indistinguishable among patients with different -202 A/C IGFBP3 genotypes. Despite similar rhGH doses, patients homozygous for the A allele presented higher IGFBP-3 sd score levels and higher mean GV in the first year of rhGH treatment than patients with AC or CC genotypes (first year GV, AA = 13.0 +/- 2.1 cm/yr, AC = 11.4 +/- 2.5 cm/yr, and CC = 10.8 +/- 1.9 cm/yr; P = 0.016). Multiple linear regression analyses demonstrated that the influence of -202 A/C IGFBP3 genotype on IGFBP-3 levels and GV during the first year of rhGH treatment was independent of other variables.


CONCLUSIONS
The -202 A allele of IGFBP3 promoter region is associated with increased IGFBP-3 levels and GV during rhGH treatment in prepubertal GHD children.
Costalonga
Everlayny Fiorot
EF
Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, Brazil.
Antonini
Sonir R
SR
Guerra-Junior
Gil
G
Mendonca
Berenice Bilharinho
BB
Arnhold
Ivo J P
IJ
Jorge
Alexander A L
AA
D000293:Adolescent; D000365:Age Determination by Skeleton; D000483:Alleles; D001827:Body Height / Q000187:drug effects; D002648:Child; D002657:Child Development / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood* / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000627:therapeutic use
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I