FBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease.

Mutations in the F-box only protein 7 gene (FBXO7), the substrate-specifying subunit of SCF E3 ubiquitin ligase complex, cause Parkinson's disease (PD)-15 (PARK15). To identify new variants, we sequenced FBXO7 cDNA in 80 Taiwanese early onset PD patients (age at onset ≤ 50) and only two known v...

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Autores principales:	Chiung-Mei Chen, I-Cheng Chen, Yi-Cheng Huang, Hsueh-Fen Juan, Ying-Lin Chen, Yi-Chun Chen, Chih-Hsin Lin, Li-Ching Lee, Chi-Mei Lee, Guey-Jen Lee-Chen, Yun-Ju Lai, Yih-Ru Wu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0dc203b0a99940399202d40dc3941328
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spelling	oai:doaj.org-article:0dc203b0a99940399202d40dc39413282021-11-25T06:08:14ZFBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease.1932-620310.1371/journal.pone.0101392https://doaj.org/article/0dc203b0a99940399202d40dc39413282014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25029497/?tool=EBIhttps://doaj.org/toc/1932-6203Mutations in the F-box only protein 7 gene (FBXO7), the substrate-specifying subunit of SCF E3 ubiquitin ligase complex, cause Parkinson's disease (PD)-15 (PARK15). To identify new variants, we sequenced FBXO7 cDNA in 80 Taiwanese early onset PD patients (age at onset ≤ 50) and only two known variants, Y52C (c.155A>G) and M115I (c.345G>A), were found. To assess the association of Y52C and M115I with the risk of PD, we conducted a case-control study in a cohort of PD and ethnically matched controls. There was a nominal difference in the Y52C G allele frequency between PD and controls (p = 0.045). After combining data from China [1], significant difference in the Y52C G allele frequency between PD and controls (p = 0.012) and significant association of G allele with decreased PD risk (p = 0.017) can be demonstrated. Upon expressing EGFP-tagged Cys52 FBXO7 in cells, a significantly reduced rate of FBXO7 protein decay was observed when compared with cells expressing Tyr52 FBXO7. In silico modeling of Cys52 exhibited a more stable feature than Tyr52. In cells expressing Cys52 FBXO7, the level of TNF receptor-associated factor 2 (TRAF2) was significantly reduced. Moreover, Cys52 FBXO7 showed stronger interaction with TRAF2 and promoted TRAF2 ubiquitination, which may be responsible for the reduced TRAF2 expression in Cys52 cells. After induced differentiation, SH-SY5Y cells expressing Cys52 FBXO7 displayed increased neuronal outgrowth. We therefore hypothesize that Cys52 variant of FBXO7 may contribute to reduced PD susceptibility in Chinese.Chiung-Mei ChenI-Cheng ChenYi-Cheng HuangHsueh-Fen JuanYing-Lin ChenYi-Chun ChenChih-Hsin LinLi-Ching LeeChi-Mei LeeGuey-Jen Lee-ChenYun-Ju LaiYih-Ru WuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e101392 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chiung-Mei Chen I-Cheng Chen Yi-Cheng Huang Hsueh-Fen Juan Ying-Lin Chen Yi-Chun Chen Chih-Hsin Lin Li-Ching Lee Chi-Mei Lee Guey-Jen Lee-Chen Yun-Ju Lai Yih-Ru Wu FBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease.
description	Mutations in the F-box only protein 7 gene (FBXO7), the substrate-specifying subunit of SCF E3 ubiquitin ligase complex, cause Parkinson's disease (PD)-15 (PARK15). To identify new variants, we sequenced FBXO7 cDNA in 80 Taiwanese early onset PD patients (age at onset ≤ 50) and only two known variants, Y52C (c.155A>G) and M115I (c.345G>A), were found. To assess the association of Y52C and M115I with the risk of PD, we conducted a case-control study in a cohort of PD and ethnically matched controls. There was a nominal difference in the Y52C G allele frequency between PD and controls (p = 0.045). After combining data from China [1], significant difference in the Y52C G allele frequency between PD and controls (p = 0.012) and significant association of G allele with decreased PD risk (p = 0.017) can be demonstrated. Upon expressing EGFP-tagged Cys52 FBXO7 in cells, a significantly reduced rate of FBXO7 protein decay was observed when compared with cells expressing Tyr52 FBXO7. In silico modeling of Cys52 exhibited a more stable feature than Tyr52. In cells expressing Cys52 FBXO7, the level of TNF receptor-associated factor 2 (TRAF2) was significantly reduced. Moreover, Cys52 FBXO7 showed stronger interaction with TRAF2 and promoted TRAF2 ubiquitination, which may be responsible for the reduced TRAF2 expression in Cys52 cells. After induced differentiation, SH-SY5Y cells expressing Cys52 FBXO7 displayed increased neuronal outgrowth. We therefore hypothesize that Cys52 variant of FBXO7 may contribute to reduced PD susceptibility in Chinese.
format	article
author	Chiung-Mei Chen I-Cheng Chen Yi-Cheng Huang Hsueh-Fen Juan Ying-Lin Chen Yi-Chun Chen Chih-Hsin Lin Li-Ching Lee Chi-Mei Lee Guey-Jen Lee-Chen Yun-Ju Lai Yih-Ru Wu
author_facet	Chiung-Mei Chen I-Cheng Chen Yi-Cheng Huang Hsueh-Fen Juan Ying-Lin Chen Yi-Chun Chen Chih-Hsin Lin Li-Ching Lee Chi-Mei Lee Guey-Jen Lee-Chen Yun-Ju Lai Yih-Ru Wu
author_sort	Chiung-Mei Chen
title	FBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease.
title_short	FBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease.
title_full	FBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease.
title_fullStr	FBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease.
title_full_unstemmed	FBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease.
title_sort	fbxo7 y52c polymorphism as a potential protective factor in parkinson's disease.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/0dc203b0a99940399202d40dc3941328
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FBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease.

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