Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants

Abstract Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is a cytoplasmic tyrosine phosphatase that is highly expressed in hematopoietic cells and in the CNS and exerts opposite effects on signal transduction by exerting a neuroprotective or proapoptotic effect. Several mutat...

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Autores principales:	So-Yeon Shim, Hye Jin Jeong, Hyo Jin Park, Eun Young Kwon, Bo Min Kim, Yang Ji Choi, Youn-Hee Choi, Su Jin Cho, Ji Ha Choi, Eun Ae Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ec5ff4c247af4a588c2fc76e7c4e4cc1
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spelling	oai:doaj.org-article:ec5ff4c247af4a588c2fc76e7c4e4cc12021-12-02T12:32:19ZFunctional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants10.1038/s41598-017-06401-x2045-2322https://doaj.org/article/ec5ff4c247af4a588c2fc76e7c4e4cc12017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06401-xhttps://doaj.org/toc/2045-2322Abstract Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is a cytoplasmic tyrosine phosphatase that is highly expressed in hematopoietic cells and in the CNS and exerts opposite effects on signal transduction by exerting a neuroprotective or proapoptotic effect. Several mutations of SHP-2 have been found in children with myeloproliferative disorders or malignant leukemia, and some of these can affect brain development. In the present study, we aimed to identify and functionally characterize genetic variations in SHP-2 in 72 preterm and 58 full-term infants and to evaluate the effect of the variations on neurodevelopment in preterm infants. Twelve genetic variations were identified. Among them, two variations in the SHP-2 promoter, g.-317C > T and g.-273G > A, were found to significantly increase promoter activity, and the frequency of g.-273G > A was higher in preterm infants than in full-term infants. Two transcription factors, NF-κB and GABPα, were found to be involved in the transcriptional regulation of SHP-2 by the two above-mentioned variations. In particular, we found that g.-273G > A was significantly associated with delayed myelination and poor motor development in preterm infants. Our results suggest that a functional promoter variation in SHP-2 is associated with spontaneous preterm birth itself as well as white matter myelination and neurodevelopment.So-Yeon ShimHye Jin JeongHyo Jin ParkEun Young KwonBo Min KimYang Ji ChoiYoun-Hee ChoiSu Jin ChoJi Ha ChoiEun Ae ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q So-Yeon Shim Hye Jin Jeong Hyo Jin Park Eun Young Kwon Bo Min Kim Yang Ji Choi Youn-Hee Choi Su Jin Cho Ji Ha Choi Eun Ae Park Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants
description	Abstract Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is a cytoplasmic tyrosine phosphatase that is highly expressed in hematopoietic cells and in the CNS and exerts opposite effects on signal transduction by exerting a neuroprotective or proapoptotic effect. Several mutations of SHP-2 have been found in children with myeloproliferative disorders or malignant leukemia, and some of these can affect brain development. In the present study, we aimed to identify and functionally characterize genetic variations in SHP-2 in 72 preterm and 58 full-term infants and to evaluate the effect of the variations on neurodevelopment in preterm infants. Twelve genetic variations were identified. Among them, two variations in the SHP-2 promoter, g.-317C > T and g.-273G > A, were found to significantly increase promoter activity, and the frequency of g.-273G > A was higher in preterm infants than in full-term infants. Two transcription factors, NF-κB and GABPα, were found to be involved in the transcriptional regulation of SHP-2 by the two above-mentioned variations. In particular, we found that g.-273G > A was significantly associated with delayed myelination and poor motor development in preterm infants. Our results suggest that a functional promoter variation in SHP-2 is associated with spontaneous preterm birth itself as well as white matter myelination and neurodevelopment.
format	article
author	So-Yeon Shim Hye Jin Jeong Hyo Jin Park Eun Young Kwon Bo Min Kim Yang Ji Choi Youn-Hee Choi Su Jin Cho Ji Ha Choi Eun Ae Park
author_facet	So-Yeon Shim Hye Jin Jeong Hyo Jin Park Eun Young Kwon Bo Min Kim Yang Ji Choi Youn-Hee Choi Su Jin Cho Ji Ha Choi Eun Ae Park
author_sort	So-Yeon Shim
title	Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants
title_short	Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants
title_full	Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants
title_fullStr	Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants
title_full_unstemmed	Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants
title_sort	functional variation of shp-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ec5ff4c247af4a588c2fc76e7c4e4cc1
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Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants

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