Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease

Abstract Parkinson’s disease (PD) is a neurodegenerative disease caused by complex interaction between genetic and environmental factors. There is a growing body of evidence of the involvement of sirtuins (SIRTs) in disease pathomechanism. SIRTs are NAD+-dependent histone deacetylases which take par...

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Autores principales:	Rita Maszlag-Török, Fanni A. Boros, László Vécsei, Péter Klivényi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bd1d6dc5b0e846eaad15fa28334ded90
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spelling	oai:doaj.org-article:bd1d6dc5b0e846eaad15fa28334ded902021-12-02T15:53:10ZGene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease10.1038/s41598-021-90059-z2045-2322https://doaj.org/article/bd1d6dc5b0e846eaad15fa28334ded902021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90059-zhttps://doaj.org/toc/2045-2322Abstract Parkinson’s disease (PD) is a neurodegenerative disease caused by complex interaction between genetic and environmental factors. There is a growing body of evidence of the involvement of sirtuins (SIRTs) in disease pathomechanism. SIRTs are NAD+-dependent histone deacetylases which take part in various cellular functions. However, available data of the relationship between SIRT gene polymorphisms and PD is limited. Our aim was to investigate the possible association of 10 SNPs identified within non-mitochondrial SIRTs, SIRT1, -2 and -6 with the risk of PD in Hungarian population, and to compare the expression level of these SIRTs between healthy controls and PD patients. Our results showed that rs3740051 and rs3818292 of SIRT1 and rs350843, rs350844, rs107251, rs350845 and rs350846 of SIRT6 show weak association with PD risk. On the contrary rs12778366 and rs3758391 of SIRT1 and rs10410544 of SIRT2 did not show association with PD. Moreover, we detected that mRNA level of SIRT1 was down-regulated, and mRNA level of SIRT6 was up-regulated, while SIRT2 mRNA level was not altered in the peripheral blood of PD patients as compared to controls. The difference in both cases was more pronounced when comparing the early-onset PD group to the control cohort. Nevertheless, mRNA level changes did not show any association with the presence of any of the investigated SNPs either in the PD or in the control group. In conclusion, our findings suggest that non-mitochondrial sirtuins, SIRT1 and -6 but not SIRT2 might contribute to the pathogenesis of PD in the Hungarian population both via their altered mRNA levels and via gene alterations identified as specific SNPs.Rita Maszlag-TörökFanni A. BorosLászló VécseiPéter KlivényiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rita Maszlag-Török Fanni A. Boros László Vécsei Péter Klivényi Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease
description	Abstract Parkinson’s disease (PD) is a neurodegenerative disease caused by complex interaction between genetic and environmental factors. There is a growing body of evidence of the involvement of sirtuins (SIRTs) in disease pathomechanism. SIRTs are NAD+-dependent histone deacetylases which take part in various cellular functions. However, available data of the relationship between SIRT gene polymorphisms and PD is limited. Our aim was to investigate the possible association of 10 SNPs identified within non-mitochondrial SIRTs, SIRT1, -2 and -6 with the risk of PD in Hungarian population, and to compare the expression level of these SIRTs between healthy controls and PD patients. Our results showed that rs3740051 and rs3818292 of SIRT1 and rs350843, rs350844, rs107251, rs350845 and rs350846 of SIRT6 show weak association with PD risk. On the contrary rs12778366 and rs3758391 of SIRT1 and rs10410544 of SIRT2 did not show association with PD. Moreover, we detected that mRNA level of SIRT1 was down-regulated, and mRNA level of SIRT6 was up-regulated, while SIRT2 mRNA level was not altered in the peripheral blood of PD patients as compared to controls. The difference in both cases was more pronounced when comparing the early-onset PD group to the control cohort. Nevertheless, mRNA level changes did not show any association with the presence of any of the investigated SNPs either in the PD or in the control group. In conclusion, our findings suggest that non-mitochondrial sirtuins, SIRT1 and -6 but not SIRT2 might contribute to the pathogenesis of PD in the Hungarian population both via their altered mRNA levels and via gene alterations identified as specific SNPs.
format	article
author	Rita Maszlag-Török Fanni A. Boros László Vécsei Péter Klivényi
author_facet	Rita Maszlag-Török Fanni A. Boros László Vécsei Péter Klivényi
author_sort	Rita Maszlag-Török
title	Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease
title_short	Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease
title_full	Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease
title_fullStr	Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease
title_full_unstemmed	Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease
title_sort	gene variants and expression changes of sirt1 and sirt6 in peripheral blood are associated with parkinson’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bd1d6dc5b0e846eaad15fa28334ded90
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Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease

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