title: Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects.
abstract: We investigated association between polymorphisms in DNA repair genes and the capacity to repair DNA damage induced by gamma-irradiation and by base oxidation in a healthy population. Irradiation-specific DNA repair rates were significantly decreased in individuals with XRCC1 Arg399Gln homozygous variant genotype (0.45 +/- 0.47 SSB/10(9) Da) than in those with wild-type genotype (1.10 +/- 0.70 SSB/10(9) Da, P=0.0006, Mann-Witney U-test). The capacity to repair oxidative DNA damage was significantly decreased among individuals with hOGG1 Ser326Cys homozygous variant genotype (0.37 +/- 0.28 SSB/10(9) Da) compared to those with wild-type genotype (0.83 +/- 0.79 SSB/10(9) Da, P=0.008, Mann-Witney U-test). Investigation of genotype combinations showed that the increasing number of variant alleles for both XRCC1 Arg399Gln and APE1 Asn148Glu polymorphisms resulted in a significant decrease of irradiation-specific repair rates (P=0.008, Kruskal-Wallis test). Irradiation-specific DNA repair rates also decreased with increasing number of variant alleles in XRCC1 Arg399Gln in combination with variant alleles for two other XRCC1 polymorphisms, Arg194Trp and Arg280His (P=0.002 and P=0.005, respectively; Kruskal-Wallis test). In a binary combination variant alleles of hOGG1 Ser326Cys and APE1 Asn148Glu polymorphisms were associated with a significant decrease in the capacity to repair DNA oxidative damage (P=0.018, Kruskal-Wallis test). In summary, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms seem to exert the predominant modulating effect on irradiation-specific DNA repair capacity and the capacity to repair DNA oxidative damage, respectively.
authors.affiliation: Institute of Experimental Medicine, Videnska 1083, 14200, Academy of Sciences of the Czech Republic, Prague, Czech Republic. pvodicka@biomed.cas.cz
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stetina
authors.forename: Veronika
authors.initials: V
authors.lastname: Polakova
authors.forename: Elena
authors.initials: E
authors.lastname: Tulupova
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.forename: Ludmila
authors.initials: L
authors.lastname: Vodickova
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Monika
authors.initials: M
authors.lastname: Hanova
authors.forename: Barbara
authors.initials: B
authors.lastname: Pardini
authors.forename: Jana
authors.initials: J
authors.lastname: Slyskova
authors.forename: Ludovit
authors.initials: L
authors.lastname: Musak
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Palma
authors.forename: Pavel
authors.initials: P
authors.lastname: Soucek
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D004249:DNA Damage; D017931:DNA Primers; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D005091:Exons; D005260:Female; D005720:Gamma Rays; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D012016:Reference Values; D012907:Smoking
chemical_list: D017931:DNA Primers