title: A Study of the Impact of Death Receptor 4 (DR4) Gene Polymorphisms in Alzheimer's Disease.
abstract: BACKGROUND
  Excessive apoptosis is believed to play a role in many degenerative and non-degenerative neurological diseases including Alzheimer's disease (AD). Much recent data suggest that apoptotic mechanisms may represent the missing link between Aβ deposition and proteolysis of tau protein. However, there is emerging evidence that apoptotic mechanisms may play a role in Alzheimer's Disease pathogenesis in the absence of overt apoptosis. TNF-related apoptosis inducing ligand receptor 1 (Death Receptor 4, DR4) might impair the apoptotic signal transduction and lead to dysregulation of the homeostasis between cell survival and cell death.
  
  
  OBJECTIVE
  The aim of our study was to further investigate the relationship between genetic variants of DR4 and Alzheimer's Disease.
  
  
  METHODS
  Case control study.
  
  
  METHODS
  Sixty-eight patients with AD were included in the study. The control group comprised 72 subjects without signs of neurodegenerative diseases, as evidenced by the examination.DNA was extracted from whole blood using the salting-out procedure. Genotypes were identified by restriction fragment length polymorphism analysis of polymerase chain reaction (PCR-RFLP) products.
  
  
  RESULTS
  We observed significant differences in the genotypic distribution of the rs6557634 polymorphism in AD patients compared with controls (p<0.05); our data suggest that the GA genotype in rs6557634 could be protective against AD (p<0.05). However, there were no significant differences between AD patients and control groups in terms of the DR4 rs20575 polymorphism (p>0.05) and the DR4 rs20576 polymorphism (p>0.05). According to haplotype analysis of the DR4 gene for rs6557634, rs20575 and rs20576 polymorphisms, GCA and GCC haplotypes might be a risk factor for AD. Also, we have shown that ACA, GGC and GGA haplotypes might be protective factors against AD.
  
  
  CONCLUSIONS
  The present results indicate for the first time the possible contribution of the DR4 gene rs6557634, rs20575, rs20576 polymorphisms in Alzheimer's Disease, which may influence susceptibility to Alzheimer's Disease.
authors.affiliation: Muğla School of Health Sciences, Muğla, Turkey.
authors.forename: Tuba Gökdoğan
authors.initials: TG
authors.lastname: Edgünlü
authors.affiliation: Department of Neurology, Mersin University School of Medicine, Mersin, Turkey.
authors.forename: Aynur
authors.initials: A
authors.lastname: Ozge
authors.affiliation: Department of Neurology, Mersin University School of Medicine, Mersin, Turkey.
authors.forename: Osman Özgür
authors.initials: OÖ
authors.lastname: Yalın
authors.affiliation: Department of Biostatistics, Gaziantep University School of Medicine, Gaziantep, Turkey.
authors.forename: Seval
authors.initials: S
authors.lastname: Kul
authors.affiliation: Department of Medical Biology and Genetics, Mersin University School of Medicine, Mersin, Turkey.
authors.forename: Mehmet Emin
authors.initials: ME
authors.lastname: Erdal
keywords: Alzheimer’s disease; death receptor 4; genetic polymorphism