Genetic testing, promoter characterization and single nucleotide polymorphisms analysis of the PPP2R2B gene

• Main Authors: Ju-yun Liu, 劉若芸
• Other Authors: Guey-Jen Lee-Chen
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/88389680454364171642

碩士 === 國立臺灣師範大學 === 生命科學研究所 === 95 === PPP2R2B is a brain-specific regulatory B subunit of protein phosphatase 2A (PP2A), whose activity is shown to be relevant to Alzheimer’s disease (AD) and other tauopathy. PP2A is a major serine/ threonine phosphatase expressed in all eukaryotic cells. It has been suggested that increased PPP2R2B expression due to CAG repeat expansion at the 5’end of the gene may result in spinocerebellar ataxia 12. However, when the expression of PP2A was suppressed, tau protein was hyper-phosphorylated in the brain, which may result in pathology like AD. We screened the PPP2R2B gene CAG repeats distribution in normal controls and in patients with various neurodegenerative diseases. The distribution of the alleles in cases did not differ significantly from that in the controls, and no expanded allele was found in either groups. However, the shorter (CAG)5~7 alleles were over-represented in patients with tremor (2.0%) and chorea (1.1%) compared with that in the controls (0.0%). In addition, a case-control study was conducted to investigate the association of four PPP2R2B promoter single nucleotide polymorphisms (SNPs) with the risk of AD or tremor. Again no significant difference in genotype and allele frequency distribution between cases and controls was observed. However, the more frequent -3170C/-2923A/-1905T/ -428G haplotype was evidently associated with AD (P = 0.019, odds ratio: 5.99; 95% CI: 1.64-38.4). The 4-kb distal fragment displayed significant decrease promoter activity compared to the 0.9-kb proximal fragment in both IMR-32 (85% activity, P = 0.014) and HEK-293 cells (82% activity, P = 0.013). Compared to the common 16-triplet allele, the rare 5~7-triplet alleles give rise to a significant decrease in the expression level in SK-N-SH, IMR-32 and HEK-293 (0.41~0.79, P = 0.000~0.040).