title: Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
abstract: BACKGROUND
  21-hydroxylase deficiency is an autosomal recessive disorder that causes glucocorticoid deficiency and increased androgen production. Treatment is based on glucocorticoid replacement; however, interindividual variability in the glucocorticoid dose required to achieve adequate hormonal control has been observed.
  
  
  OBJECTIVE
  The present study aimed to evaluate the association between polymorphic variants involved inglucocorticoid action and/or metabolism and the mean daily glucocorticoid dose in 21-hydroxylase deficiency patients.
  
  
  METHODS
  We evaluated 53 patients with classical forms of 21-hydroxylase deficiency who were receiving cortisone acetate. All patients were between four and six years of age and had normal androgen levels.
  
  
  RESULTS
  The P450 oxidoreductase A503V, HSD11B1 rs12086634, and CYP3A7*1C variants were found in 19%, 11.3% and 3.8% of the patients, respectively. The mean ± SD glucocorticoid dose in patients with the CYP3A7*1C and wild-type alleles was 13.9 ± 0.8 and 19.5 ± 3.2 mg/m²/d, respectively. We did not identify an association between the P450 oxidoreductase or HSD11B1 allelic variants and the mean glucocorticoid dose.
  
  
  CONCLUSIONS
  Patients carrying the CYP3A7*1C variant required a significantly lower mean glucocorticoid dose. Indeed, the CYP3A7*1C allele accounted for 20% of the variability in the cortisone acetate dose. The analysis of genes involved in glucocorticoid metabolism may be useful in the optimization of treatment of 21-hydroxylase deficiency.
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM 42, Disciplina de Endocrinologia da Faculdade de Medicina da Universidad, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Ricardo P P
authors.initials: RP
authors.lastname: Moreira
authors.forename: Alexander A L
authors.initials: AA
authors.lastname: Jorge
authors.forename: Larissa G
authors.initials: LG
authors.lastname: Gomes
authors.forename: Laura C
authors.initials: LC
authors.lastname: Kaupert
authors.forename: João
authors.initials: J
authors.lastname: Massud Filho
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Tânia A S S
authors.initials: TA
authors.lastname: Bachega
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003348:Cortisone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D020249:Hormone Replacement Therapy; D006801:Humans; D007223:Infant; D008297:Male; D010088:Oxidoreductases / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D005938:Glucocorticoids; D010088:Oxidoreductases; D003348:Cortisone