PPP2R2B CAG repeat length in the Han Chinese in Taiwan: Association analyses in neurological and psychiatric disorders and potential functional implications

Chiung Mei Chen, Yi Ting Hou, Ju Yun Liu, Yih Ru Wu, Chih Hsin Lin, Hon Chung Fung, Wen Chuin Hsu, Yuying Hsu, Shen Hung Lee, Hsiu Mei Hsieh-Li, Ming Tsan Su, Shui Tein Chen, Hsien Yuan Lane, Guey Jen Lee-Chen

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

PPP2R2B, a protein widely expressed in neurons throughout the brain, regulates the protein phosphatase 2A (PP2A) activity for the microtubule-associated protein tau and other substrates. Altered PP2A activity has been implicated in spinocerebellar ataxia 12, Alzheimer's disease (AD), and other tauopathies. Through a case-control study and a reporter assay, we investigated the association of PPP2R2B CAG repeat polymorphism with Taiwanese AD, essential tremor (ET), Parkinson's disease (PD), and schizophrenia and clarified the functional implication of this polymorphism. The distribution of the alleles was not significantly different between patients and controls, with 68.6-76.1% alleles at lengths of 10, 13, and 16 triplets. No expanded alleles were detected in either group. However, the frequency of the individuals carrying the short 5-, 6-, and 7-triplet alleles was notably higher in patients with AD (5/180 [2.8%], Fisher's exact test, P = 0.003; including 2 homozygotes) and ET (4/132 [3.0%], Fisher's exact test, P < 0.001) than in the controls (1/625 [0.2%]). The PPP2R2B transcriptional activity was significantly lower in the luciferase reporter constructs containing the (CAG)5-7 allele than in those containing the common 10-, 13-, and 16-triplet alleles in both neuroblastoma and embryonic kidney cells. Therefore, our preliminary results suggest that the PPP2R2B gene CAG repeat polymorphism may be functional and may, in part, play a role in conferring susceptibility to AD and ET in Taiwan.

Original languageEnglish
Pages (from-to)124-129
Number of pages6
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume150
Issue number1
DOIs
Publication statusPublished - 2009 Jan 5

Keywords

  • Alzheimer's disease
  • CAG repeat polymorphism
  • Essential tremor
  • PPP2R2B
  • Promoter assay

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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