title: Polymorphisms in the DNA repair genes XPD (ERCC2) and XPF (ERCC4) are not associated with sporadic late-onset Alzheimer's disease.
abstract: Nucleotide excision repair (NER) is the most versatile mechanism of DNA repair, recognizing and dealing a variety of helix-distorting lesions. Xeroderma pigmentosum group D (XPD) and group F (XPF) are essential participants in NER pathway. There is evidence that two common polymorphisms of XPD gene (g.22541C>A; exon 6 and g.35931A>C; Lys>Gln; exon 23) may be associated with differential DNA repair activities. Alzheimer's disease (AD) is characterized by progressive neuronal loss correlated in time with the symptoms of disease considered. Although deficient DNA repair was proposed in the etiology of AD by several researchers, polymorphisms of DNA repair genes have not been studied in AD yet. We conducted a case-control study including 97 patients with AD and age- and sex-matched 101 control subjects to examine the role of genetic polymorphisms of XPD and XPF (g.30028T>C; exon 11) as a risk factor for AD. The frequencies of the XPD/exon 6, XPD/exon 23, and XPF/exon 11 variant alleles in our control group were 0.41, 0.35, and 0.35, respectively. No significant association was observed between the variant alleles of XPD/exon 6 (OR=0.94, 95% CI=0.63-1.41), XPD/exon 23 (OR=1.24, 95% CI=0.82-1.86) and XPF/exon 11 (OR=1.08, 95% CI=0.72-1.64) and AD. Our results suggest that the polymorphic variants of these NER genes do not contribute to the risk of developing AD.
authors.affiliation: Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Capa, Istanbul, Turkey. sdabbasoglu@yahoo.com
authors.forename: Semra
authors.initials: S
authors.lastname: Dogru-Abbasoglu
authors.forename: Muzeyyen
authors.initials: M
authors.lastname: Inceoglu
authors.forename: Hande
authors.initials: H
authors.lastname: Parildar-Karpuzoglu
authors.forename: Hasmet A
authors.initials: HA
authors.lastname: Hanagasi
authors.forename: Berrin
authors.initials: B
authors.lastname: Karadag
authors.forename: Hakan
authors.initials: H
authors.lastname: Gurvit
authors.forename: Murat
authors.initials: M
authors.lastname: Emre
authors.forename: Gulcin
authors.initials: G
authors.lastname: Aykac-Toker
authors.forename: Mujdat
authors.initials: M
authors.lastname: Uysal
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012306:Risk; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C095888:xeroderma pigmentosum group F protein; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human