title: PPP2R2B CAG repeat length in the Han Chinese in Taiwan: Association analyses in neurological and psychiatric disorders and potential functional implications.
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.
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital, Chang-Gung University College of Medicine, Taipei, Taiwan.
authors.forename: Chiung-Mei
authors.initials: CM
authors.lastname: Chen
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Hou
authors.forename: Ju-Yun
authors.initials: JY
authors.lastname: Liu
authors.forename: Yih-Ru
authors.initials: YR
authors.lastname: Wu
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Lin
authors.forename: Hon-Chung
authors.initials: HC
authors.lastname: Fung
authors.forename: Wen-Chuin
authors.initials: WC
authors.lastname: Hsu
authors.forename: Yuying
authors.initials: Y
authors.lastname: Hsu
authors.forename: Shen-Hung
authors.initials: SH
authors.lastname: Lee
authors.forename: Hsiu-Mei
authors.initials: HM
authors.lastname: Hsieh-Li
authors.forename: Ming-Tsan
authors.initials: MT
authors.lastname: Su
authors.forename: Shui-Tein
authors.initials: ST
authors.lastname: Chen
authors.forename: Hsien-Yuan
authors.initials: HY
authors.lastname: Lane
authors.forename: Guey-Jen
authors.initials: GJ
authors.lastname: Lee-Chen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D003001:Cloning, Molecular; D020329:Essential Tremor / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D054648:Protein Phosphatase 2 / Q000235:genetics*; D013624:Taiwan; D018911:Trinucleotide Repeats
chemical_list: D009419:Nerve Tissue Proteins; C505936:PPP2R2B protein, human; D054648:Protein Phosphatase 2