MKRN3 circulating levels in Prader-Willi syndrome: a pilot study.
Hypogonadism
MKRN3
Prader Willi
Puberty
Journal
Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
received:
28
01
2022
accepted:
03
07
2022
pubmed:
20
7
2022
medline:
5
10
2022
entrez:
19
7
2022
Statut:
ppublish
Résumé
Hypogonadism in Prader-Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect. MKRN3, a maternal imprinted gene located on 15q11.2-q13 region, encodes makorin ring finger protein 3, whose deficiency causes precocious puberty, an extremely rare symptom in PWS. This study aimed to evaluate MKRN3 levels in patients with PWS and to analyze its correlation with sexual hormone levels, insulin resistance and Body Mass Index (BMI). We performed an observational cross-sectional study and enrolled 80 patients with genetically confirmed diagnosis of PWS with median age of 9.6 years. MKRN3 levels were measurable in 49 PWS patients with a geometric mean of 34.9 ± 22 pg/ml (median: 28.4). Unmeasurable levels of MKRN3 were found in 31 patients. No statistically significant differences were found between patients with and without measurable MKRN3 levels for any clinical, biochemical, or genetic characteristics. However, MKRN3 levels were inversely correlated with HOMA-IR index (p: 0.005) and HbA1c (p: 0.046) values. No statistically significant correlations were found between MKRN3 and LH, estradiol and testosterone concentrations, pubertal development and genetic defect, whereas a direct correlation with FSH was found (p: 0.007). The typical genetic defect of PWS should lead to unmeasurable levels of the MKRN3 protein due to the inactivation of the paternal allele. Measurable circulating MKRN3 could suggest the possible involvement of tissue-specific imprinting mechanisms and other regulatory factors in gene expression. Correlations with HOMA-IR index, HbA1c, and FSH suggest peripheral actions of MKRN3, but future studies are warranted to investigate this topic.
Identifiants
pubmed: 35854182
doi: 10.1007/s40618-022-01860-0
pii: 10.1007/s40618-022-01860-0
doi:
Substances chimiques
Glycated Hemoglobin A
0
Testosterone
3XMK78S47O
Estradiol
4TI98Z838E
Follicle Stimulating Hormone
9002-68-0
MKRN3 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2165-2170Informations de copyright
© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).
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