Association of serum components of the GH-IGFs-IGFBPs system with GHR-exon 3 polymorphism in normal and idiopathic short stature children

BALLERINI MG; DOMENÉ HM; SCAGLIA P ; MARTÍNEZ A; KESELMAN A ; JASPER HG ; ROPELATO MG

GROWTH HORMONE & IGF RESEARCH : OFFICIAL JOURNAL OF THE GROWTH HORMONE RESEARCH SOCIETY AND THE INTERNATIONAL IGF RESEARCH SOCIETY.

CHURCHILL LIVINGSTONE

Lugar: ESCOCIA; Año: 2013 vol. 26 p. 229 - 236

1096-6374

Objective: To investigate the possible association of circulating components of GH-IGFs-IGFBPs system with the GHR-exon 3 genotype in normal and idiopathic short stature (ISS) children. Design: Descriptive, cross-sectional study in normal and ISS children. Subjects andmethods: 192 normal and 81 ISS children (age: 5?17 years)were included. Serum IGF-I, IGFBP3, ALS and GHBP levels were measured. GHR-exon 3 polymorphism (GHRd3) was analyzed by multiplex PCR assay. Normal and ISS children were divided according to GHR-exon 3 genotype: homozygous for the full-length GHR isoform (GHRfl) and carriers of one or two copies of the GHRd3 allele. Results: GHRd3 genotype distribution (fl:fl/fl:d3/d3:d3,%) in normal (60:34:6) and ISS (64:32:4)was similar and reached Hardy?Weinberg equilibrium. ISS children had significantly reduced levels of GHBP and GH-dependent factors as compared to controls (p b 0.0001). Within the normal group, homozygous carriers of the GHRfl allele had significantly higherGHBP serumlevels than those with one or two copies of the GHRd3 allele (Mean ± SEM; GHRfl: 3.2 ± 0.2 vs GHRd3: 2.7 ± 0.2 nmol/L, p = 0.04). No other significant association with GHR exon 3 polymorphism was found in either the normal or the ISS groups. Conclusions: GHR exon 3 polymorphism is distributed similarly in normal and ISS children, however only normal homozygous children for GHRfl allele showed higherGHBP levels. The lack of association between GHBP and GHR polymorphism in ISS childrenmight be related to the heterogeneity of this group,where potential defects in GH receptor action may result in partial GH insensitivity.To investigate the possible association of circulating components of GH-IGFs-IGFBPs system with the GHR-exon 3 genotype in normal and idiopathic short stature (ISS) children. Design: Descriptive, cross-sectional study in normal and ISS children. Subjects andmethods: 192 normal and 81 ISS children (age: 5?17 years)were included. Serum IGF-I, IGFBP3, ALS and GHBP levels were measured. GHR-exon 3 polymorphism (GHRd3) was analyzed by multiplex PCR assay. Normal and ISS children were divided according to GHR-exon 3 genotype: homozygous for the full-length GHR isoform (GHRfl) and carriers of one or two copies of the GHRd3 allele. Results: GHRd3 genotype distribution (fl:fl/fl:d3/d3:d3,%) in normal (60:34:6) and ISS (64:32:4)was similar and reached Hardy?Weinberg equilibrium. ISS children had significantly reduced levels of GHBP and GH-dependent factors as compared to controls (p b 0.0001). Within the normal group, homozygous carriers of the GHRfl allele had significantly higherGHBP serumlevels than those with one or two copies of the GHRd3 allele (Mean ± SEM; GHRfl: 3.2 ± 0.2 vs GHRd3: 2.7 ± 0.2 nmol/L, p = 0.04). No other significant association with GHR exon 3 polymorphism was found in either the normal or the ISS groups. Conclusions: GHR exon 3 polymorphism is distributed similarly in normal and ISS children, however only normal homozygous children for GHRfl allele showed higherGHBP levels. The lack of association between GHBP and GHR polymorphism in ISS childrenmight be related to the heterogeneity of this group,where potential defects in GH receptor action may result in partial GH insensitivity.