ECE2015 Eposter Presentations Adrenal cortex (94 abstracts)
Background: Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder caused by 21-hydroxylase deficiency in 95% of all cases. Two main clinical subtypes: the classical (manifested after birth, or in early newborn period) and the late onset (LO) phenotype (manifested commonly during puberty). The lifelong glucocorticoid (GC) supplementation is essential in therapy of these patients. Response to GC therapy is individual and partly genetically determined.
Objective: Our aim was to study the effect of three well-known polymorphisms (SNPs; BclI, N363S, A3669G) of the GR on therapy, clinical, and laboratory parameters in gene in adult Hungarian patients with 21-hydroxylase deficiency.
Patients and methods: The diagnosis of 21-hydroxylase deficiency was based on clinical, laboratory, and molecular genetic tests including the identification of the most common CYP21A2 gene mutations and determination of the allelic copy number (CN) of the CYP21A2 gene. In 93 patients (54 classical and 39 late-onset, age: 28.8±13.7 years) with 21-hyídroxylase deficiency the BclI and N363S polymorphisms were measured using allele-specific PCR, the A3669G polymorphism and the CN variations were detected by real-time qPCR. Allele frequencies of GR polymorphisms were compared to a Hungarian, control population (n=160). Association between GR SNPs and clinical, hormone laboratory, and GC supplementation dosage was studied.
Results: Allelic frequency of the GR polymorphisms did not differ from those observed in control population and did not associate with clinical, laboratory parameters or dosage of the GC supplementation. The CN of the CYP21A2 in both groups of patients a significantly negatively correlated with GC therapy (P=0.03).
Conclusion: The GR polymorphisms associated sensitivity against glucocorticoids is not a major factor in determination of the dose of glucocorticoid supplementation. The CYP21A2 CN measurement is a rapid, cheap and sensitive method for prediction the GC need in patients with 21-hydroxylase deficiency.