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Sökning: WFRF:(Aulinas A.)

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  • Valassi, E., et al. (författare)
  • A polymorphism in the CYP17A1 gene influences the therapeutic response to steroidogenesis inhibitors in Cushing's syndrome
  • 2017
  • Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664. ; 87:5, s. 433-439
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Steroidogenesis inhibitors, such as ketoconazole (KTZ) and metyrapone (MTP), are used to lower hypercortisolism in patients with Cushing's syndrome (CS). Cortisol normalization is not reached in all patients taking these medications. Objective: To test the hypothesis that variants in genes affecting steroidogenesis contribute to different responses to KTZ and/or MTP in patients with CS. Patients and methods: Fifty-four CS patients (46 women; mean [SD] age, 39.712.7; 83% with Cushing's disease [CD] and 17% with an adrenal adenoma) preoperatively treated with KTZ (20%), MTP (37%) or a combination of both (43%). Thirty-nine of these (72%) were described in a previous study investigating the outcome of preoperative treatment with KTZ or MTP in CS patients. Following single-nucleotide polymorphisms (SNPs) were analysed: rs6410 (CYP11B1 gene), rs1799998 and rs4546 (CYP11B2 gene), and rs6163 (CYP17A1 gene). The associations between SNPs and cortisol levels at the end of medical treatment were evaluated. Results: Normalization of urinary free cortisol (UFC) was achieved in 50% of patients after 5months of treatment. Patients carrying the CC genotype of SNP rs6163 were more likely to be controlled than AC/AA (OR 0.25 [95%CI, 0.075-0.88]; P=.031). When only patients reaching eucortisolism after medical treatment were analysed, median interquartile range (IQR) duration of treatment was shorter in patients carrying the CC genotype of SNP rs6163 as compared to AA/AC carriers (4 [4.57]months vs 5.2 [6.1]months; P=.026). Conclusions: A polymorphism in the CYP17A1 gene was associated with the response to steroidogenesis inhibitors in CS. Genetic differences in the steroidogenic enzymes might account for inter-individual variations in the responsiveness to adrenal-blocking agents.
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