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Genetic Variants of BMP2 and Their Association with the Risk of Non-Syndromic Tooth Agenesis

Non-syndromic tooth agenesis (or non-syndromic congenitally missing tooth) is one of the most common congenital defects in humans affecting the craniofacial function and appearance. Single nucleotide polymorphisms (SNPs) have been associated with an individual’s susceptibility to these anomalies. Th...

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Autores principales: Lu, Yun, Qian, Yajing, Zhang, Jinglu, Gong, Miao, Wang, Yuting, Gu, Ning, Ma, Lan, Xu, Min, Ma, Junqing, Zhang, Weibing, Pan, Yongchu, Wang, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928851/
https://www.ncbi.nlm.nih.gov/pubmed/27362534
http://dx.doi.org/10.1371/journal.pone.0158273
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author Lu, Yun
Qian, Yajing
Zhang, Jinglu
Gong, Miao
Wang, Yuting
Gu, Ning
Ma, Lan
Xu, Min
Ma, Junqing
Zhang, Weibing
Pan, Yongchu
Wang, Lin
author_facet Lu, Yun
Qian, Yajing
Zhang, Jinglu
Gong, Miao
Wang, Yuting
Gu, Ning
Ma, Lan
Xu, Min
Ma, Junqing
Zhang, Weibing
Pan, Yongchu
Wang, Lin
author_sort Lu, Yun
collection PubMed
description Non-syndromic tooth agenesis (or non-syndromic congenitally missing tooth) is one of the most common congenital defects in humans affecting the craniofacial function and appearance. Single nucleotide polymorphisms (SNPs) have been associated with an individual’s susceptibility to these anomalies. The aim of the present study was therefore to investigate the roles of the potentially functional SNPs of BMP2 in the occurrence of tooth agenesis. Overall, four potentially functional SNPs of BMP2 (rs15705, rs235768, rs235769 and rs3178250) were selected, and their associations with the susceptibility of tooth agenesis were evaluated in a case-control study of 335 non-syndromic tooth agenesis cases and 444 healthy controls. The SNPs rs15705 and rs3178250 were found to be associated with an individual’s risk of tooth agenesis (P = 0.046 and P = 0.039, respectively). Both SNPs showed an increased risk of mandibular incisor agenesis (rs15705, AA/AC vs. CC = 1.58, 95% CI = [1.06–2.34], P = 0.024; rs3178250, TT/TC vs. CC = 1.60, 95% CI = [1.08–2.37], P = 0.020). Bioinformatics analysis indicated that these two SNPs located at the 3’-untranslated region (3’-UTR) of BMP2 might alter the binding ability of miR-1273d and miR-4639-5p, respectively, which was confirmed by luciferase activity assays in the 293A and COS7 cell lines (P < 0.001 in 293A and P < 0.01 in COS7 for miR-1273d; and P < 0.001 in both cells for miR-4639-5p). Furthermore, BMP2 mRNA expression decreased after transfecting either miR-1273d or miR-4639-5p into these two cell lines (P < 0.01 in 293A and P < 0.001 in COS7 for miR-1273d, and P < 0.01 in both cell lines for miR-4639-5p). Taken together, our findings indicate that rs15705 and rs317250 are associated with the susceptibility of non-syndromic tooth agenesis by possibly affecting miRNAs and mRNA interaction.
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spelling pubmed-49288512016-07-18 Genetic Variants of BMP2 and Their Association with the Risk of Non-Syndromic Tooth Agenesis Lu, Yun Qian, Yajing Zhang, Jinglu Gong, Miao Wang, Yuting Gu, Ning Ma, Lan Xu, Min Ma, Junqing Zhang, Weibing Pan, Yongchu Wang, Lin PLoS One Research Article Non-syndromic tooth agenesis (or non-syndromic congenitally missing tooth) is one of the most common congenital defects in humans affecting the craniofacial function and appearance. Single nucleotide polymorphisms (SNPs) have been associated with an individual’s susceptibility to these anomalies. The aim of the present study was therefore to investigate the roles of the potentially functional SNPs of BMP2 in the occurrence of tooth agenesis. Overall, four potentially functional SNPs of BMP2 (rs15705, rs235768, rs235769 and rs3178250) were selected, and their associations with the susceptibility of tooth agenesis were evaluated in a case-control study of 335 non-syndromic tooth agenesis cases and 444 healthy controls. The SNPs rs15705 and rs3178250 were found to be associated with an individual’s risk of tooth agenesis (P = 0.046 and P = 0.039, respectively). Both SNPs showed an increased risk of mandibular incisor agenesis (rs15705, AA/AC vs. CC = 1.58, 95% CI = [1.06–2.34], P = 0.024; rs3178250, TT/TC vs. CC = 1.60, 95% CI = [1.08–2.37], P = 0.020). Bioinformatics analysis indicated that these two SNPs located at the 3’-untranslated region (3’-UTR) of BMP2 might alter the binding ability of miR-1273d and miR-4639-5p, respectively, which was confirmed by luciferase activity assays in the 293A and COS7 cell lines (P < 0.001 in 293A and P < 0.01 in COS7 for miR-1273d; and P < 0.001 in both cells for miR-4639-5p). Furthermore, BMP2 mRNA expression decreased after transfecting either miR-1273d or miR-4639-5p into these two cell lines (P < 0.01 in 293A and P < 0.001 in COS7 for miR-1273d, and P < 0.01 in both cell lines for miR-4639-5p). Taken together, our findings indicate that rs15705 and rs317250 are associated with the susceptibility of non-syndromic tooth agenesis by possibly affecting miRNAs and mRNA interaction. Public Library of Science 2016-06-30 /pmc/articles/PMC4928851/ /pubmed/27362534 http://dx.doi.org/10.1371/journal.pone.0158273 Text en © 2016 Lu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lu, Yun
Qian, Yajing
Zhang, Jinglu
Gong, Miao
Wang, Yuting
Gu, Ning
Ma, Lan
Xu, Min
Ma, Junqing
Zhang, Weibing
Pan, Yongchu
Wang, Lin
Genetic Variants of BMP2 and Their Association with the Risk of Non-Syndromic Tooth Agenesis
title Genetic Variants of BMP2 and Their Association with the Risk of Non-Syndromic Tooth Agenesis
title_full Genetic Variants of BMP2 and Their Association with the Risk of Non-Syndromic Tooth Agenesis
title_fullStr Genetic Variants of BMP2 and Their Association with the Risk of Non-Syndromic Tooth Agenesis
title_full_unstemmed Genetic Variants of BMP2 and Their Association with the Risk of Non-Syndromic Tooth Agenesis
title_short Genetic Variants of BMP2 and Their Association with the Risk of Non-Syndromic Tooth Agenesis
title_sort genetic variants of bmp2 and their association with the risk of non-syndromic tooth agenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928851/
https://www.ncbi.nlm.nih.gov/pubmed/27362534
http://dx.doi.org/10.1371/journal.pone.0158273
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