PPP2R2B CAG repeat length in the Han Chinese in Taiwan: Association analyses in neurological and psychiatric disorders and potential functional implications.
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.
Chen
Chiung-Mei
CM
Department of Neurology, Chang Gung Memorial Hospital, Chang-Gung University College of Medicine, Taipei, Taiwan.
Hou
Yi-Ting
YT
Liu
Ju-Yun
JY
Wu
Yih-Ru
YR
Lin
Chih-Hsin
CH
Fung
Hon-Chung
HC
Hsu
Wen-Chuin
WC
Hsu
Yuying
Y
Lee
Shen-Hung
SH
Hsieh-Li
Hsiu-Mei
HM
Su
Ming-Tsan
MT
Chen
Shui-Tein
ST
Lane
Hsien-Yuan
HY
Lee-Chen
Guey-Jen
GJ
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
D009419:Nerve Tissue Proteins; C505936:PPP2R2B protein, human; D054648:Protein Phosphatase 2