The Presence of Clitoromegaly in the Nonclassical Form of 21-Hydroxylase Deficiency Could Be Partially Modulated by the CAG Polymorphic Tract of the Androgen Receptor GeneReportar como inadecuado




The Presence of Clitoromegaly in the Nonclassical Form of 21-Hydroxylase Deficiency Could Be Partially Modulated by the CAG Polymorphic Tract of the Androgen Receptor Gene - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Background

In the nonclassical form NC, good correlation has been observed between genotypes and 17OH-progesterone 17-OHP levels. However, this correlation was not identified with regard to the severity of hyperandrogenic manifestations, which could depend on interindividual variability in peripheral androgen sensitivity. Androgen action is modulated by the polymorphic CAG tract nCAG of the androgen receptor AR gene and by polymorphisms in 5α-reductase type 2 SRD5A2 enzyme, both of which are involved in the severity of hyperandrogenic disorders.

Objectives

To analyze whether nCAG-AR and SRD5A2 polymorphisms influence the severity of the nonclassical phenotype.

Patients

NC patients n = 114 diagnosed by stimulated-17OHP ≥10 ng-mL were divided into groups according to the beginning of hyperandrogenic manifestations pediatric and adolescent-adult and CYP21A2 genotypes C-C: homozygosis for mild mutations; A-C: compound heterozygosis for severe-mild mutations.

Methods

CYP21A2 mutations were screened by allelic-specific PCR, MLPA and-or sequencing. HpaII-digested and HpaII-undigested DNA samples underwent GeneScan analysis to study nCAG, and the SRD5A2 polymorphisms were screened by RLFP.

Results

Mean nCAG did not differ among pediatric, adolescent-adult and asymptomatic subjects. In the C-C genotype, we observed a significantly lower frequency of longer CAG alleles in pediatric patients than in adolescent-adults p = 0.01. In patients carrying the A-C genotype, the frequencies of shorter and longer CAG alleles did not differ between pediatric patients and adolescent-adults p>0.05. Patients with clitoromegaly had significantly lower weighted CAG biallelic mean than those without it: 19.1±2.7 and 21.6±2.5, respectively p = 0.007, independent of the CYP21A2 genotype-s severity. The SRD5A2 polymorphisms were not associated with the variability of hyperandrogenic NC phenotypes.

Conclusions

In this series, we observed a modulatory effect of the CAG-AR tract on clinical manifestations of the NC form. Although the NC form is a monogenic disorder, our preliminary data suggested that the interindividual variability of the hyperandrogenic phenotype could arise from polygenic interactions.



Autor: Vivian Oliveira Moura-Massari , Flávia Siqueira Cunha , Larissa Garcia Gomes, Diogo Bugano Diniz Gomes, José Antônio Miguel Ma

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados