Evaluation of the Poly(ADP-ribose) Polymerase-1 Gene Variants in Alzheimer's Disease

被引：46

作者：

Liu, Hsin-Ping ^{[2
]}

Lin, Wei-Yong ^{[1
,3
]}

Wu, Bor-Tsang ^{[4
]}

Liu, Shu-Hsiang ^{[5
]}

Wang, Wen-Fu ^{[6
]}

Tsai, Chon-Haw ^{[7
,8
]}

Lee, Chun-Cheng ^{[1
,4
]}

Tsai, Fuu-Jen ^{[1
,5
,9
]}

机构：

[1] China Med Univ Hosp, Dept Med Res, Taichung 404, Taiwan

[2] China Med Univ, Grad Inst Acupuncture Sci, Taichung, Taiwan

[3] China Med Univ, Grad Inst Integrated Med, Taichung, Taiwan

[4] China Med Univ, Sch Phys Therapy, Taichung, Taiwan

[5] Asia Univ, Dept Biotechnol, Taichung, Taiwan

[6] Chang Hua Christian Hosp, Dept Neurol, Changhua, Taiwan

[7] China Med Univ, Grad Inst Neural & Cognit Sci, Taichung, Taiwan

[8] China Med Univ Hosp, Dept Neurol, Taichung 404, Taiwan

[9] China Med Univ, Grad Inst Chinese Med Sci, Taichung, Taiwan

来源：

JOURNAL OF CLINICAL LABORATORY ANALYSIS | 2010年 / 24卷 / 03期

关键词：

Alzheimer's disease; PARP-1; polymorphism; AMYLOID PRECURSOR PROTEIN; DNA STRAND BREAKS; TRANSGENIC MICE; HAPLOTYPE RECONSTRUCTION; OXIDATIVE STRESS; RAT HIPPOCAMPUS; CORE PROTEIN; NITRIC-OXIDE; BETA; POLYMORPHISMS;

D O I：

10.1002/jcla.20379

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

1001 ;

摘要：

Amyloid peptide is thought to play a critical role in neuronal death in Alzheimer's disease (AD), most likely through oxidative stress. Free radical-related injury leads to DNA breaks, which subsequently activates the repair enzyme poly(ADP-ribose) polymerase-1 (PARP-1). In this study, the relationship between genetic variants situated at the PARP-1 gene and AD development was investigated. We performed a case and control study from a Taiwanese population enrolled 120 AD patients and 111 healthy controls by using a polymerase chain reaction restriction fragment length polymorphism approach for two PARP-1 exonic polymorphisms, 414C/T (rs1805404) and 2456T/C (rs1136410), corresponding to protein residues at positions 81Asp/Asp and 762Val/Ala. There were no significant differences in allele or genotype frequencies for either PARP-1 gene variant between the case and control groups; however, upon analysis of the haplotype distribution, four haplotypes (Hts) were identified. We found that the distributions of Ht3-TT and Ht4-CC were significantly associated with an increased risk of AD (P<0.0001), whereas the Ht1-TC haplotype showed a protective effect for cases compared with the control group (P<0.05). These results reveal that the PARP-1 gene is highly associated with AD susceptibility and might contribute to a critical mechanism that mediates cell survival or death as a response to cytotoxic stress. J. Clin. Lab. Anal. 24:182-186, 2010. (C) 2010 Wiley-Liss, Inc.

引用

页码：182 / 186

页数：5

共 37 条

[31] DNA strand breakage, activation of poly(ADP-ribose) synthetase, and cellular energy depletion are involved in the cytotoxicity in macrophages and smooth muscle cells exposed to peroxynitrite [J].