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

Chiung Mei Chen, I. G. 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

研究成果: 雜誌貢獻文章

8 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
文章編號e101392
期刊PloS one
9
發行號7
DOIs
出版狀態已發佈 - 2014 七月 16

    指紋

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

引用此

Chen, C. M., Chen, I. G., Huang, Y. C., Juan, H. F., Chen, Y. L., Chen, Y. C., Lin, C. H., Lee, L. C., Lee, C. M., Lee-Chen, G. J., Lai, Y. J., & Wu, Y. R. (2014). FBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease. PloS one, 9(7), [e101392]. https://doi.org/10.1371/journal.pone.0101392