A Ser326Cys polymorphism in the DNA repair gene hOGG1 is not associated with sporadic Alzheimer's disease.
Oxidative damage accumulates in the DNA of the human brain over time, and is supposed to play a critical role in the pathogenesis of Alzheimer's disease (AD). It has been suggested that the brain in AD might be subjected to the double insult of increased oxidative stress, as well as deficiencies in repair mechanisms responsible for the removal of oxidized bases. The type of damage that is most likely to occur in neuronal cells is oxidative DNA damage which is primarily removed by the base excision repair (BER) pathway, and a decrease in BER activity was observed in post-mortem brain regions of AD individuals, especially in the activity of 8-oxoguanine DNA glycosylase. There is evidence that the Ser326Cys polymorphism of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene is associated with a reduced DNA repair activity. However, although a deficient BER was proposed in the etiology of AD by several authors, polymorphisms of BER genes have not been studied in AD yet. We performed a case-control study including 178 patients with sporadic AD (sAD) and 146 matched controls to evaluate the role of the Ser326Cys polymorphism as a risk factor for sAD. In the present study we failed to find any association between allele (chi2=0.03, p=0.86) or genotype (chi2=0.25, p=0.882) frequencies of hOGG1 Ser326Cys and the risk of sAD. Present results suggest that the Ser326Cys polymorphism of the hOGG1 gene is not an independent risk factor for sAD.
Coppedè
Fabio
F
Department of Neurosciences, University of Pisa, Via Roma 67, 56126 Pisa, Italy. f.coppede@geog.unipi.it
Mancuso
Michelangelo
M
Lo Gerfo
Annalisa
A
Manca
Maria Laura
ML
Petrozzi
Lucia
L
Migliore
Lucia
L
Siciliano
Gabriele
G
Murri
Luigi
L
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D019943:Amino Acid Substitution / Q000235:genetics; D001921:Brain / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D003553:Cystine / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D045647:DNA Glycosylases / Q000235:genetics*; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012694:Serine / Q000235:genetics
D005819:Genetic Markers; D012694:Serine; D003553:Cystine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human