La caracterización de un polimorfismo en la región promotora del gen IGFBP3 podría mejorar la utilidad de la medición de IGBP-3 en el diagnostico diferencial de la talla baja en la infancia

P. SCAGLIA; H. DOMENÉ; A. MARTÍNEZ; A. KESELMAN; V. PIPMAN; V. BENGOLEA; L. KARABATAS; G. ROPELATO; G. BALLERINI; J. HEINRICH; H. JASPER

Lima, Perú.

Congreso; XX Reunión anual de la Sociedad Latinoamericana de Endocrinología Pediátrica.; 2008

Sociedad Latinoamericana de Endocrinología Pediátrica

Variability of IGFBP-3 levels is related to polymorphic variants at the promoter region of IGFBP3 gene. The aims of this study were to determine this effect in N, ISS, and GHD children and to evaluate if genotyping the IGFBP3 gene may improve the efficiency of IGFBP-3 measurement in the diagnosis of GHD. We enrolled 190 N (4.9-16.6 y, -1.96 to 2.53 SDS), 91 ISS (1.8-17.5 y, -4.8 to -1.6 SDS) and 28 GHD (2.0-17.6 y, -8.4 to -2.4 SDS). IGFBP-3 levels were measured by IRMA, and two SNPs of IGFBP3 gene by RFLP (-202 C/A; -185 C/T). One-way ANOVA (A) followed by Tukey´s and linear trend (LT) tests and ROC curves were used for statistical analysis. IGFBP-3 levels were significantly different among -202 IGFBP3 genotypes, both in N [AA: 0.33±0.15 (X±SEM, SDS), AC: 0.14±0.10, CC: -0.30±0.11; A: p=0.0021; AA>CC, p<0.01; AC>CC, p<0.05; LT: p=0.0026) and ISS children (AA: -0.02±0.28, AC: -0.85±0.19, CC: -1.30±0.27; A: p=0.0102; AA>CC, p<0.01; LT: p=0.0025). In GHD there was a non-significant trend (AA:-1.56±0.81, AC:-2.69±0.94, CC:-4.11±0.89). The diagnostic efficiency (DE) of IGFBP-3 measurement for GHD diagnosis in Tanner I stage patients (73 ISS; 25 GHD), was 79.4 %, sensitivity (Se) 82.2% and specificity (Sp) 70.8%, (cut-off:2.7 µg/ml). Using genotype-specific cut-off levels (3.55, 2.70, and 1.34 µg/ml for AA, AC, and CC, respectively) there was an improvement of DE 86.6%, Se 90.4%, and Sp 75.0%. This study extend the association of -202 IGFBP3 polymorphism with IGFBP-3 serum levels in ISS, resulting in an improvement of its measurement in the diagnosis of GHD in a clinical setting.