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A variant in the SCN10A enhancer may affect human mechanical pain sensitivity

Expression of Nav1.8, encoded by SCN10A, can affect pain transmission and thus mediate the human pain phenotype. In the current study, we assessed whether the variant rs6801957, located in the SCN10A enhancer region, may have the potential to affect human pain. Through dual-luciferase reporter assay...

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Autores principales: Duan, Guangyou, Sun, Jiaoli, Li, Ningbo, Zheng, Hua, Guo, Shanna, Zhang, Yuhao, Wang, Qingli, Ying, Ying, Zhang, Mi, Huang, Penghao, Zhang, Xianwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858611/
https://www.ncbi.nlm.nih.gov/pubmed/29448912
http://dx.doi.org/10.1177/1744806918763275
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author Duan, Guangyou
Sun, Jiaoli
Li, Ningbo
Zheng, Hua
Guo, Shanna
Zhang, Yuhao
Wang, Qingli
Ying, Ying
Zhang, Mi
Huang, Penghao
Zhang, Xianwei
author_facet Duan, Guangyou
Sun, Jiaoli
Li, Ningbo
Zheng, Hua
Guo, Shanna
Zhang, Yuhao
Wang, Qingli
Ying, Ying
Zhang, Mi
Huang, Penghao
Zhang, Xianwei
author_sort Duan, Guangyou
collection PubMed
description Expression of Nav1.8, encoded by SCN10A, can affect pain transmission and thus mediate the human pain phenotype. In the current study, we assessed whether the variant rs6801957, located in the SCN10A enhancer region, may have the potential to affect human pain. Through dual-luciferase reporter assays in 293T cells, we found that the SCN10A enhancer A (Enh-A) increased the activity of the SCN10A promoter (P < 0.05). Additionally, in a cohort of 309 healthy women, mutant rs6801957 A/A was found to have a significant association with decreased human experimental mechanical pain sensitivity (P < 0.05). We then found that mutant genotype A/A suppressed the increased effect of Enh-A compared with wild-type G/G (P < 0.05). The association between rs6801957 and human experimental mechanical pain sensitivity was further validated in a larger cohort of 1005 women (P < 0.05). In conclusion, these results demonstrated that the variant rs6801957 and Enh-A may affect SCN10A gene expression and play an important role in human mechanical pain sensitivity.
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spelling pubmed-58586112018-03-22 A variant in the SCN10A enhancer may affect human mechanical pain sensitivity Duan, Guangyou Sun, Jiaoli Li, Ningbo Zheng, Hua Guo, Shanna Zhang, Yuhao Wang, Qingli Ying, Ying Zhang, Mi Huang, Penghao Zhang, Xianwei Mol Pain Research Article Expression of Nav1.8, encoded by SCN10A, can affect pain transmission and thus mediate the human pain phenotype. In the current study, we assessed whether the variant rs6801957, located in the SCN10A enhancer region, may have the potential to affect human pain. Through dual-luciferase reporter assays in 293T cells, we found that the SCN10A enhancer A (Enh-A) increased the activity of the SCN10A promoter (P < 0.05). Additionally, in a cohort of 309 healthy women, mutant rs6801957 A/A was found to have a significant association with decreased human experimental mechanical pain sensitivity (P < 0.05). We then found that mutant genotype A/A suppressed the increased effect of Enh-A compared with wild-type G/G (P < 0.05). The association between rs6801957 and human experimental mechanical pain sensitivity was further validated in a larger cohort of 1005 women (P < 0.05). In conclusion, these results demonstrated that the variant rs6801957 and Enh-A may affect SCN10A gene expression and play an important role in human mechanical pain sensitivity. SAGE Publications 2018-02-15 /pmc/articles/PMC5858611/ /pubmed/29448912 http://dx.doi.org/10.1177/1744806918763275 Text en © The Author(s) 2018 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Article
Duan, Guangyou
Sun, Jiaoli
Li, Ningbo
Zheng, Hua
Guo, Shanna
Zhang, Yuhao
Wang, Qingli
Ying, Ying
Zhang, Mi
Huang, Penghao
Zhang, Xianwei
A variant in the SCN10A enhancer may affect human mechanical pain sensitivity
title A variant in the SCN10A enhancer may affect human mechanical pain sensitivity
title_full A variant in the SCN10A enhancer may affect human mechanical pain sensitivity
title_fullStr A variant in the SCN10A enhancer may affect human mechanical pain sensitivity
title_full_unstemmed A variant in the SCN10A enhancer may affect human mechanical pain sensitivity
title_short A variant in the SCN10A enhancer may affect human mechanical pain sensitivity
title_sort variant in the scn10a enhancer may affect human mechanical pain sensitivity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858611/
https://www.ncbi.nlm.nih.gov/pubmed/29448912
http://dx.doi.org/10.1177/1744806918763275
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