IMPE2023 Free Communications Adrenals and HPA Axis 2 (4 abstracts)
Differential methylation of CYP11B1 in girls with high DHEAS levels
Fernando Rodríguez 1 , Diana Ponce 1 , José Patricio Miranda 2,3 , José Luis Santos 2 , Gordon B. Cutler Jr 4 , Ana Pereira 5 , Germán Iñiguez 1 & Verónica Mericq 1
1Institute of Maternal and Child Research, School of Medicine, Universidad de Chile, Santiago, Chile. 2Department of Nutrition, Diabetes, and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. 3Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile & Universidad de Chile, Santiago, Chile. 4Gordon Cutler Consultancy LLC, Deltaville, Virginia, USA. 5Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile
Context: Premature adrenarche in girls is defined biochemically by an increase in adrenal androgen (DHEA and DHEAS) levels above the age-specific reference range before age 8 years. Recently, increased levels of 11-oxyandrogens have also been observed in girls with premature adrenarche. On the other hand, epigenetic control of some genes that code for enzymes that participate in the synthetic pathway to 11-oxyandrogens (e.g., CYP11B1) has been described.
Objective: To determine whether circulating DHEAS levels in girls at Tanner breast stage 1 are associated with the methylation status of CYP11B1.
Design: Ninety-seven healthy girls followed since the age of 3 years were classified, according to DHEAS serum concentration at age 6-7 years, as normal DHEAS (< 42 μg/dL [75th percentile for population]) or high DHEAS (≥ 42 μg/dL). At Tanner stage 2, methylation status of CYP11B1 was analyzed in genomic DNA from peripheral blood leukocytes by Melting Curve Analysis Methylation assay.
Results: Significantly lower methylation levels were detected in the CYP11B1 gene in girls with high vs normal serum DHEAS. In addition, we found a significant inverse correlation between CYP11B1 methylation and insulin level at Tanner 1 and BMI at Tanner 1 and 2, in the whole cohort.
Conclusion: These results suggest that a lower methylation of CYP11B1 could be a mechanism contributing to increased concentrations of 11-oxyandrogens in premature adrenarche.
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