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P3‐230: Alterations in the expression of genes important in Alzheimer's disease (APP, presenilin 1, tau) in the HFE knockout mouse model of the iron disorder hemochromatosis
Author(s) -
Johnstone Daniel,
Graham Ross,
Trinder Deborah,
Scott Rodney,
Olynyk John,
Milward Elizabeth
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1797
Subject(s) - presenilin , apolipoprotein e , allele , haplotype , disease , alzheimer's disease , hemochromatosis , genotype , hereditary hemochromatosis , cognitive decline , dementia , mutation , genetics , age of onset , medicine , biology , gene
Background: Although the etiology of Alzheimer disease (AD) has not yet been identified, many mechanisms have been implied in neurodegenerative pathogenesis. GSTP1 has an important role on oxidative stress, GAPDH may have role on neuronal apoptosis and GAB2 on neuronal differentiation. APOE affect lipid metabolism and has been shown as the most well established genetic factor for Alzheimer disease. In this study, we have analyzed GAPDH, GSTP1, and GAB2 gene polymorphisms and their interactions with the APOE*E4 allele in a sample of late onset AD. Methods: DNA was extracted from peripheral blood leukocytes of AD patients and elderly controls. We performed genotypic analysis by using allelic discrimination on Real-Time PCR. We have analyzed 7 single nucleotide polymorphisms (SNPs) on 4 different genes (APOE, GAPDH, GSTP1 and GAB2) in a sample of 139 AD patients and 74 normal elderly controls. Results: As expected, the APOE*E2 allele variant was more frequently found among controls and the APOE*E4 allele was associated with the diagnosis of AD (P 0,00127). In AD group, we found significant associations with the GSTP1 rs1138272 and the GAB2 rs2373115 polymorphisms. Regarding the GSTP1 gene, the CT genotype was found exclusively in the control group (P 0,003). Suggesting that this genotype may yield a protective effect on control group. The combination of the C allele and the APOE-E4 genotype conferred a even stronger association with AD (P 0,007). Regarding the GAB2 gene, the presence of the TT genotype was associated with AD (P 0,002) and the GG genotype associated with at least one *E4 allele resulted in increased risk for AD (P 0,005). Conclusions: Considering the multifactorial nature of AD including both environmental and genetics features, and the fact that except for apolipoprotein E (APOE) polymorphisms little is known about the genetic causes of AD, other genes with relevant roles in neuronal homeostasis, such as oxidative stress, neuronal apoptosis and neuronal differentiation need to be investigated. If those associations prove consistent in even larger samples, the underlying biological roles of GSTP1 and GAB2 will require further clarification.