GHR AND IGFBP-3 GENE POLYMORPHISMS. EFFECTS ON IN VITRO IGF TERNARY COMPLEX FORMATION (TCF).

GUTIÉRREZ M; SCAGLIA P; DOMENÉ H; PIPMAN V; BENGOLEA S; BEDECARRAS P; KARABATAS L; MARTINEZ A; KESELMAN A; ROPELATO M; BALLERINI G; HEINRICH J; JASPER H

Viña del Mar, Chile

Congreso; XVIII Annual Meeting of the Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP); 2006

Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP)

Introduction: IGF-I and IGFBP-3 normal levels show great variability. In part, this might be caused by polymorphisms in their genes. Besides, polymorphisms affecting the response to GH (presence or absence of exon 3 in GHR gene) might have an additional effect, and together modify TCF. Objective: verify if GHR and IGFBP3 gene polymorphisms affect TCF. Subjects and methods: study approved by the 3 IRBs involved.105 normal subjects aged 5-16 yr. IGF-I measured by RIA, IGFBP-3 by IRMA, IGFBP3 gene polymorphisms (positions -185 and -202) and of exon 3 of GHR gene by methods in Scaglia P. et al, this meeting. TCF by incubation with 125I-IGF-I and subsequent cross-linking. Statistical analysis by one-way ANOVAs and Pearson´s correlations. Results: IGF-I, IGFBP-3 and TCF increased (p<0.0001) with age and pubertal stage (Tanner [T] ). IGF-I (ng/ml) from 101±5 (TI) to 277±13 (TIV), IGFBP-3 (µg/ml) from 4.2±0.1 (TI) to 6.3±0.2 (TIV) and TCF (%) from 21±0.01 (TI) to 44±0.02 (TIV) (mean ± sem). IGF-I and IGFBP-3 correlated with TCF (both in absolute values and SDS, p<0.001). Following a codominant mode of inheritance IGFBP-3 levels were significantly reduced by the -202 polymorphism (CC genotype) and by the GHR polymorphism (FL/DEL+DEL/DEL genotypes) (Scaglia P. et al, this meeting). TCF was reduced (p=0.011) by the joint presence of both polymorphisms. Conclusions: TCF is affected by age and pubertal status. Persistence of significant correlations between IGF-I and IGFBP-3 with TCF in abscence of these confounding factors points to the action of other regulatory factors. Among them might be polymorphisms of the IGFBP3 and GHR genes affecting IGFBP-3 serum levels and TCF