Evaluation of the poly(ADP-ribose) polymerase-1 gene variants in Alzheimer's disease.
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.
Liu
Hsin-Ping
HP
Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan.
Lin
Wei-Yong
WY
Wu
Bor-Tsang
BT
Liu
Shu-Hsiang
SH
Wang
Wen-Fu
WF
Tsai
Chon-Haw
CH
Lee
Chun-Cheng
CC
Tsai
Fuu-Jen
FJ
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013624:Taiwan
C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases