Abstract
PurposeGenotype–phenotype correlation in congenital 21 hydroxylase deficiency is strong but by no means absolute. Indeed, clinical and hormonal features may vary among patients carrying similar CYP21A2 mutations, suggesting that modifier genes may contribute to the phenotype. Aim of the present study was to evaluate whether polymorphisms in the p450 oxidoreductase (POR) gene may affect clinical features in patients with 21 hydroxylase deficiencyMethodsSequencing of the POR gene was performed in 96 patients with 21 hydroxylase deficiency (49 classic, 47 non-classic) and 43 control subjects.ResultsPrevalence of POR polymorphisms in patients with 21 hydroxylase was comparable to controls and known databases. The rs2228104 polymorphism was more frequently associated with non-classic vs classic 21 hydroxylase deficiency (allelic risk 7.09; 95% C.I. 1.4–29.5, p < 0.05). Classic 21 hydroxylase-deficient carriers of the minor allele in the rs2286822/rs2286823 haplotype presented more frequently the salt-wasting form (allelic risk 1.375; 95% C.I. 1.138–1.137), more severe Prader stage at birth (allelic risk 3.85; 95% C.I. 3.78–3.92), higher ACTH levels, and younger age at diagnosis.ConclusionsPolymorphisms in the POR gene are associated with clinical features of 21 hydroxylase deficiency both as regards predisposition to classic vs non-classic forms and severity of classic adrenal hyperplasia.
Highlights
Congenital adrenal hyperplasia due to 21 hydroxylase deficiency ranks among the most frequent endocrine genetic defects, and considerable efforts have been expended toIt is conceivable that other factors may influence 21 hydroxylase enzyme activity and contribute to the variability of clinical features among different enzyme defects
The present study shows that polymorphisms in the P450 oxidoreductase (POR) gene are associated with the phenotype of patients with congenital adrenal hyperplasia, a novel finding in the pathophysiology of 21 hydroxylase deficiency
POR is a flavoprotein which subserves several microsomal enzymatic reactions, most notably those deputized to drug metabolism and steroid biosynthesis [20]
Summary
Congenital adrenal hyperplasia due to 21 hydroxylase deficiency ranks among the most frequent endocrine genetic defects, and considerable efforts have been expended to. It is conceivable that other factors may influence 21 hydroxylase enzyme activity and contribute to the variability of clinical features among different enzyme defects. P450 oxidoreductase (POR), a flavoprotein involved in several microsomal reactions including 21 hydroxylation [7], is one of the most likely candidates. Interest in POR stems for the fact that mutations in POR lead to deranged steroidogenesis with sexual ambiguity and cortisol deficiency [8, 9]. In addition to these enzyme-disrupting mutations, the POR gene is highly polymorphic and variants have been associated with altered 21 hydroxylase and 17 hydroxylase/17,20 lyase activity [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
