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Candidate Genes for Age at Menarche Are Associated With Uterine Leiomyoma

Age at menarche (AAM) is an important marker of the pubertal development and function of the hypothalamic–pituitary–ovarian system. It was reported as a possible factor for a risk of uterine leiomyoma (UL). However, while more than 350 loci for AAM have been determined by genome-wide association stu...

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Autores principales: Ponomarenko, Irina, Reshetnikov, Evgeny, Polonikov, Alexey, Verzilina, Irina, Sorokina, Inna, Yermachenko, Anna, Dvornyk, Volodymyr, Churnosov, Mikhail
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863975/
https://www.ncbi.nlm.nih.gov/pubmed/33552117
http://dx.doi.org/10.3389/fgene.2020.512940
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author Ponomarenko, Irina
Reshetnikov, Evgeny
Polonikov, Alexey
Verzilina, Irina
Sorokina, Inna
Yermachenko, Anna
Dvornyk, Volodymyr
Churnosov, Mikhail
author_facet Ponomarenko, Irina
Reshetnikov, Evgeny
Polonikov, Alexey
Verzilina, Irina
Sorokina, Inna
Yermachenko, Anna
Dvornyk, Volodymyr
Churnosov, Mikhail
author_sort Ponomarenko, Irina
collection PubMed
description Age at menarche (AAM) is an important marker of the pubertal development and function of the hypothalamic–pituitary–ovarian system. It was reported as a possible factor for a risk of uterine leiomyoma (UL). However, while more than 350 loci for AAM have been determined by genome-wide association studies (GWASs) to date, no studies of these loci for their association with UL have been conducted so far. In this study, we analyzed 52 candidate loci for AAM for possible association with UL in a sample of 569 patients and 981 controls. The results of the study suggested that 23 out of the 52 studied polymorphisms had association with UL. Locus rs7759938 LIN28B was individually associated with the disease according to the dominant model. Twenty loci were associated with UL within 11 most significant models of intergenic interactions. Nine loci involved in 16 most significant models of interactions between single-nucleotide polymorphism (SNP), induced abortions, and chronic endometritis were associated with UL. Among the 23 loci associated with UL, 16 manifested association also with either AAM (7 SNPs) or height and/or body mass index (BMI) (13 SNPs). The above 23 SNPs and 514 SNPs linked to them have non-synonymous, regulatory, and expression quantitative trait locus (eQTL) significance for 35 genes, which play roles in the pathways related to development of the female reproductive organs and hormone-mediated signaling [false discovery rate (FDR) ≤ 0.05]. This is the first study reporting associations of candidate genes for AAM with UL.
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spelling pubmed-78639752021-02-06 Candidate Genes for Age at Menarche Are Associated With Uterine Leiomyoma Ponomarenko, Irina Reshetnikov, Evgeny Polonikov, Alexey Verzilina, Irina Sorokina, Inna Yermachenko, Anna Dvornyk, Volodymyr Churnosov, Mikhail Front Genet Genetics Age at menarche (AAM) is an important marker of the pubertal development and function of the hypothalamic–pituitary–ovarian system. It was reported as a possible factor for a risk of uterine leiomyoma (UL). However, while more than 350 loci for AAM have been determined by genome-wide association studies (GWASs) to date, no studies of these loci for their association with UL have been conducted so far. In this study, we analyzed 52 candidate loci for AAM for possible association with UL in a sample of 569 patients and 981 controls. The results of the study suggested that 23 out of the 52 studied polymorphisms had association with UL. Locus rs7759938 LIN28B was individually associated with the disease according to the dominant model. Twenty loci were associated with UL within 11 most significant models of intergenic interactions. Nine loci involved in 16 most significant models of interactions between single-nucleotide polymorphism (SNP), induced abortions, and chronic endometritis were associated with UL. Among the 23 loci associated with UL, 16 manifested association also with either AAM (7 SNPs) or height and/or body mass index (BMI) (13 SNPs). The above 23 SNPs and 514 SNPs linked to them have non-synonymous, regulatory, and expression quantitative trait locus (eQTL) significance for 35 genes, which play roles in the pathways related to development of the female reproductive organs and hormone-mediated signaling [false discovery rate (FDR) ≤ 0.05]. This is the first study reporting associations of candidate genes for AAM with UL. Frontiers Media S.A. 2021-01-22 /pmc/articles/PMC7863975/ /pubmed/33552117 http://dx.doi.org/10.3389/fgene.2020.512940 Text en Copyright © 2021 Ponomarenko, Reshetnikov, Polonikov, Verzilina, Sorokina, Yermachenko, Dvornyk and Churnosov. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Ponomarenko, Irina
Reshetnikov, Evgeny
Polonikov, Alexey
Verzilina, Irina
Sorokina, Inna
Yermachenko, Anna
Dvornyk, Volodymyr
Churnosov, Mikhail
Candidate Genes for Age at Menarche Are Associated With Uterine Leiomyoma
title Candidate Genes for Age at Menarche Are Associated With Uterine Leiomyoma
title_full Candidate Genes for Age at Menarche Are Associated With Uterine Leiomyoma
title_fullStr Candidate Genes for Age at Menarche Are Associated With Uterine Leiomyoma
title_full_unstemmed Candidate Genes for Age at Menarche Are Associated With Uterine Leiomyoma
title_short Candidate Genes for Age at Menarche Are Associated With Uterine Leiomyoma
title_sort candidate genes for age at menarche are associated with uterine leiomyoma
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863975/
https://www.ncbi.nlm.nih.gov/pubmed/33552117
http://dx.doi.org/10.3389/fgene.2020.512940
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