Differential methylation pattern in pubertal girls associated with biochemical premature adrenarche
Biochemical premature adrenarche is defined by elevated serum DHEAS [≥40 μg/dL] before age 8 y in girls. This condition is receiving more attention due to its association with obesity, hyperinsulinemia, dyslipidemia, and polycystic ovary syndrome. Nevertheless, the link between early androgen excess and these risk factors remains unknown. Epigenetic modifications, and specifically DNA methylation, have been associated with the initiation and progression of numerous disorders, including obesity and insulin resistance. The aim of this study was to determine if prepubertal androgen exposure is associated with a different methylation profile in pubertal girls. Eighty-six healthy girls were studied. At age 7 y, anthropometric measurements were begun and DHEAS levels were determined. Girls were classified into Low DHEAS (LD) [<42 μg/dL] and High DHEAS (HD) [≥42 μg/dL] groups. At Tanner stages 2 and 4 a DNA methylation microarray was performed to identify differentially methylated CpG positions (DMPs) between HD and LD groups. We observed a differential methylation pattern between pubertal girls with and without biochemical PA. Moreover, a set of DNA methylation markers, selected by the LASSO method, successfully distinguished between HD and LD girls regardless of Tanner stage. Additionally, a subset of these markers were significantly associated with glucose-related measures such as insulin level, HOMA-IR, and glycaemia. This pilot study provides evidence consistent with the hypothesis that high DHEAS concentration, or its hormonally active metabolites, may induce a unique blood methylation signature in pubertal girls, and that this methylation pattern is associated with altered glucose metabolism.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Epigenetics - 18(2023), 1 vom: 02. Dez., Seite 2200366 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ponce, Diana [VerfasserIn] |
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| Links: |
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| Themen: |
57B09Q7FJR |
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| Anmerkungen: |
Date Completed 17.04.2023 Date Revised 03.05.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/15592294.2023.2200366 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM355575310 |
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| 520 | |a Biochemical premature adrenarche is defined by elevated serum DHEAS [≥40 μg/dL] before age 8 y in girls. This condition is receiving more attention due to its association with obesity, hyperinsulinemia, dyslipidemia, and polycystic ovary syndrome. Nevertheless, the link between early androgen excess and these risk factors remains unknown. Epigenetic modifications, and specifically DNA methylation, have been associated with the initiation and progression of numerous disorders, including obesity and insulin resistance. The aim of this study was to determine if prepubertal androgen exposure is associated with a different methylation profile in pubertal girls. Eighty-six healthy girls were studied. At age 7 y, anthropometric measurements were begun and DHEAS levels were determined. Girls were classified into Low DHEAS (LD) [<42 μg/dL] and High DHEAS (HD) [≥42 μg/dL] groups. At Tanner stages 2 and 4 a DNA methylation microarray was performed to identify differentially methylated CpG positions (DMPs) between HD and LD groups. We observed a differential methylation pattern between pubertal girls with and without biochemical PA. Moreover, a set of DNA methylation markers, selected by the LASSO method, successfully distinguished between HD and LD girls regardless of Tanner stage. Additionally, a subset of these markers were significantly associated with glucose-related measures such as insulin level, HOMA-IR, and glycaemia. This pilot study provides evidence consistent with the hypothesis that high DHEAS concentration, or its hormonally active metabolites, may induce a unique blood methylation signature in pubertal girls, and that this methylation pattern is associated with altered glucose metabolism | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a DHEAS | |
| 650 | 4 | |a Premature adrenarche | |
| 650 | 4 | |a glucose metabolism | |
| 650 | 4 | |a methylation | |
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| 650 | 7 | |a Dehydroepiandrosterone Sulfate |2 NLM | |
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| 700 | 1 | |a Rodríguez, Fernando |e verfasserin |4 aut | |
| 700 | 1 | |a Miranda, José P |e verfasserin |4 aut | |
| 700 | 1 | |a Binder, Alexandra M |e verfasserin |4 aut | |
| 700 | 1 | |a Santos, José L |e verfasserin |4 aut | |
| 700 | 1 | |a Michels, Karin B |e verfasserin |4 aut | |
| 700 | 1 | |a Cutler, Gordon B |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Pereira, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a Iñiguez, Germán |e verfasserin |4 aut | |
| 700 | 1 | |a Mericq, Verónica |e verfasserin |4 aut | |
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