Evaluation of the poly(ADP-ribose) polymerase-1 gene variants in Alzheimer's disease.

Abstract:

: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.

journal_name

J Clin Lab Anal

authors

Liu HP,Lin WY,Wu BT,Liu SH,Wang WF,Tsai CH,Lee CC,Tsai FJ

doi

10.1002/jcla.20379

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

182-6

issue

3

eissn

0887-8013

issn

1098-2825

journal_volume

24

pub_type

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