Association between Bone Mineral Density and VDR and IGF-1 Genes Polymorphisms in Patients with Congenital Arenal Hyperplasia (CAH-21OH) Treated with Glucocorticoids

PICOTTO, G.; MARTIN, S.; MUÑOZ, L.; PEREZ, A.; DÍAZ DE BARBOZA, G.; SOBRERO, G.; OCHETTI, M.; CARPENTIERI, A.; SILVANO, L.; SIGNORINO, M.; RUPEREZ, C.; BERTOLOTTO, P.; PELLIZAS, C.; DEL MAR MONTESINOS, M.; TOLOSA DE TALAMONI, N.; MIRAS, M.

Montevideo

Encuentro; XXIII Annual Meeting, SLEP Montevideo, Uruguay; 2012

Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP)

Introduction: Patients with Congenital Adrenal Hyperplasia (CAH) with glucorticoid therapy (GC) may present bone metabolism alterations. Vitamin D receptor (VDR) and IGF-I gene polymorphisms are considered as genetic markers of bone mineral density (BMD). Objectives: To analyze VDR and IGF-I gene polymorphisms in CAH patients and the relationships with bone markers andBMD. Methods: Sixty six CAH patients treated with GC were classifiedin two groups according to the presence of an adequate (Acl) or inadequate (Icl) clinical and biochemical control. We evaluated BMD by DEXA, bone markers (osteocalcin and β-crosslaps), VDR gene polymorphisms (Bsm I and Fok I sites) and IGF1, by PCR-RFLP. Statistical analysis: Chi, Wilcoxon or Mann-Whitney and Krustal Wallis tests. Results: Patients carrying FF genotypes showed thelowest z-score of spine BMD (FF: ?1.41; Ff: 0.13; ff: ?0.10; P<0.05).The analysis of IGF-1 gene polymorphisms revealed that the frequencyof allele 192 in the Icl group was lower vs controls. CAH patients with genotype 0/0 (absence of allele 192) presented higher values of β-crosslaps (0/0: 1.57 ng/mL; 0/192: 1.24 ng/mL; 192/192: 1.02 ng/mL; P<0.05) and lower BMDs (0/0: 0.84 gr/cm2; 0/192: 1.10 gr/cm2; 192/192: 1.00 gr/cm2; P=0.05). Conclusions: CAH patients lacking allele 192 have an altered bone turnover and inadequateresponse to therapy. In addition, patients with genotype FF have the lowest bone mass. The evaluation of these polymorphisms may be useful to predict as predictors of low bone mass in patients with CAH.