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 and762Val/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. © 2010 Wiley‐Liss, Inc.