Dataset Information

The Role of SNPs in the Pathogenesis of Idiopathic Central Precocious Puberty in Girls.

ABSTRACT: The initiation of puberty is a crucial timepoint of development, with its disruptions being associated with multiple physical and psychological complications. Idiopathic Central Precocious Puberty (iCPP) has been correlated with Single-Nucleotide Polymorphisms (SNPs) of certain genes that are implicated in various steps of the process of pubertal onset. The aim of this review was to gather current knowledge on SNPs of genes associated with iCPP. We searched articles published on the PubMed, EMBASE and Google Scholar platforms and gathered current literature. KISS1, KISS1R, PLCB1, PRKCA, ITPR1, MKRN3, HPG axis genes, NPVF/NPFFR1, DLK1, KCNK9Q, LIN28B, PROK2R, IGF-1, IGF2, IGF-1R, IGF-2R, IGFBP-3, insulin, IRS-1, LEP/LEPR, PPARγ2, TAC3, TACR3, Estrogen receptors, CYP3A4 and CYP19A1 were studied for implication in the development of precocious puberty. SNPs discovered in genes KISS1, KISS1R, PLCB1, MKRN3, NPVF, LIN28B, PROK2R, IRS-1 TAC3, and CYP3A4 were significantly correlated with CPP, triggering or protecting from CPP. Haplotype (TTTA)13 in CYP19A1 was a significant contributor to CPP. Further investigation of the mechanisms implicated in the pathogenesis of CPP is required to broaden the understanding of these genes' roles in CPP and possibly initiate targeted therapies.

SUBMITTER: Toutoudaki K

PROVIDER: S-EPMC10047240 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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The Role of SNPs in the Pathogenesis of Idiopathic Central Precocious Puberty in Girls.

Toutoudaki Konstantina K Paltoglou George G Papadimitriou Dimitrios T DT Eleftheriades Anna A Tsarna Ermioni E Christopoulos Panagiotis P

Children (Basel, Switzerland) 20230225 3

The initiation of puberty is a crucial timepoint of development, with its disruptions being associated with multiple physical and psychological complications. Idiopathic Central Precocious Puberty (iCPP) has been correlated with Single-Nucleotide Polymorphisms (SNPs) of certain genes that are implicated in various steps of the process of pubertal onset. The aim of this review was to gather current knowledge on SNPs of genes associated with iCPP. We searched articles published on the PubMed, EMBA ...[more]

PMID: 36980008

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Project description:BackgroundGenetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the onset of puberty or the susceptibility to a wide range of diseases later in life. The present study aims to investigate changes in genomic DNA methylation profiles associated with pubertal onset analyzing human peripheral blood leukocytes from three different groups of subjects: 19 girls with central precocious puberty (CPP), 14 healthy prepubertal girls matched by age and 13 healthy pubertal girls matched by pubertal stage. For this purpose, the comparisons were performed between pre- and pubertal controls to identify changes in normal pubertal transition and CPP versus pre- and pubertal controls.ResultsAnalysis of methylation changes associated with normal pubertal transition identified 1006 differentially methylated CpG sites, 86% of them were found to be hypermethylated in prepubertal controls. Some of these CpG sites reside in genes associated with the age of menarche or transcription factors involved in the process of pubertal development. Analysis of methylome profiles in CPP patients showed 65% and 55% hypomethylated CpG sites compared with prepubertal and pubertal controls, respectively. In addition, interestingly, our results revealed the presence of 43 differentially methylated genes coding for zinc finger (ZNF) proteins. Gene ontology and IPA analysis performed in the three groups studied revealed significant enrichment of them in some pathways related to neuronal communication (semaphorin and gustation pathways), estrogens action, some cancers (particularly breast and ovarian) or metabolism (particularly sirtuin).ConclusionsThe different methylation profiles of girls with normal and precocious puberty indicate that regulation of the pubertal process in humans is associated with specific epigenetic changes. Differentially methylated genes include ZNF genes that may play a role in developmental control. In addition, our data highlight changes in the methylation status of genes involved in signaling pathways that determine the migration and function of GnRH neurons and the onset of metabolic and neoplastic diseases that may be associated with CPP in later life.

Project description:BackgroundRecent studies demonstrated that changes in DNA methylation (DNAm) and inactivation of two imprinted genes (MKRN3 and DLK1) alter the onset of female puberty. We aimed to investigate the association of DNAm profiling with the timing of human puberty analyzing the genome-wide DNAm patterns of peripheral blood leukocytes from ten female patients with central precocious puberty (CPP) and 33 healthy girls (15 pre- and 18 post-pubertal). For this purpose, we performed comparisons between the groups: pre- versus post-pubertal, CPP versus pre-pubertal, and CPP versus post-pubertal.ResultsAnalyzing the methylome changes associated with normal puberty, we identified 120 differentially methylated regions (DMRs) when comparing pre- and post-pubertal healthy girls. Most of these DMRs were hypermethylated in the pubertal group (99%) and located on the X chromosome (74%). Only one genomic region, containing the promoter of ZFP57, was hypomethylated in the pubertal group. ZFP57 is a transcriptional repressor required for both methylation and imprinting of multiple genomic loci. ZFP57 expression in the hypothalamus of female rhesus monkeys increased during peripubertal development, suggesting enhanced repression of downstream ZFP57 target genes. Fourteen other zinc finger (ZNF) genes were related to the hypermethylated DMRs at normal puberty. Analyzing the methylome changes associated with CPP, we demonstrated that the patients with CPP exhibited more hypermethylated CpG sites compared to both pre-pubertal (81%) and pubertal (89%) controls. Forty-eight ZNF genes were identified as having hypermethylated CpG sites in CPP.ConclusionMethylome profiling of girls at normal and precocious puberty revealed a widespread pattern of DNA hypermethylation, indicating that the pubertal process in humans is associated with specific changes in epigenetically driven regulatory control. Moreover, changes in methylation of several ZNF genes appear to be a distinct epigenetic modification underlying the initiation of human puberty.

Project description:BackgroundPrecocious puberty (PP) in girls is traditionally defined as the onset of breast development before the age of 8 years. The specific biomarkers of premature thelarche (PT) and central precocious puberty (CPP) girls are uncertain, and little is known about their metabolic characteristics driven by perfluorinated compounds (PFCs) and clinical phenotype. This study aimed to screen specific biomarkers of PT and CPP and elucidate their underlying pathogenesis. The relationships of clinical phenotype-serum PFCs-metabolic characteristics were also explored to reveal the relationship between PFCs and the occurrence and development of PT and CPP.MethodsNuclear magnetic resonance (NMR)-based cross-metabolomics strategy was performed on serum from 146 PP (including 30 CPP, 40 PT, and 76 unspecified PP) girls and 64 healthy girls (including 36 prepubertal and 28 adolescent). Specific biomarkers were screened by the uni- and multivariate statistical analyses. The relationships between serum PFCs and clinical phenotype were performed by correlation analysis and weighted gene co-expression network analysis to explore the link of clinical phenotype-PFCs-metabolic characteristics in PT and CPP.ResultsThe disordered trend of pyruvate and butyrate metabolisms (metabolites mapped as formate, ethanol, and 3-hydroxybutyrate) were shared and kept almost consistent in PT and CPP. Eight and eleven specific biomarkers were screened for PT and CPP, respectively. The area under curve of specific biomarker combination was 0.721 in CPP vs. prepubertal, 0.972 in PT vs. prepubertal, 0.646 in CPP vs. prepubertal integrated adolescent, and 0.822 in PT vs. prepubertal integrated adolescent, respectively. Perfluoro-n-heptanoic acid and perfluoro-n-hexanoic acid were statistically different between PT and CPP. Estradiol and prolactin were significantly correlated with PFCs in CPP and PT. Clinical phenotypes and PFCs drive the metabolic characteristics and cause metabolic disturbances in CPP and PT.ConclusionsThe elevation of formate, ethanol, and 3-hydroxybutyrate may serve as the early diagnostic indicator for PP in girls. But the stratification of PP still needs to be further determined based on the specific biomarkers. Specific biomarkers of CPP and PT exhibited good sensitivity and can facilitate the classification diagnosis of CPP and PT. PFC exposure is associated with endocrine homeostasis imbalance. PFC exposure and/or endocrine disturbance directly or indirectly drive metabolic changes and form overall metabolic network perturbations in CPP and PT.

Dataset Information

The Role of SNPs in the Pathogenesis of Idiopathic Central Precocious Puberty in Girls.

Publications

The Role of SNPs in the Pathogenesis of Idiopathic Central Precocious Puberty in Girls.

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