We investigated association between polymorphisms in DNA repair genes and the capacity to repair DNA damage induced by γ-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/109 Da) than in those with wild-type genotype (1.10 ± 0.70 SSB/109 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/109 Da) compared to those with wild-type genotype (0.83 ± 0.79 SSB/109 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. © 2007 Oxford University Press.

Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects

Pardini B.;
2007-01-01

Abstract

We investigated association between polymorphisms in DNA repair genes and the capacity to repair DNA damage induced by γ-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/109 Da) than in those with wild-type genotype (1.10 ± 0.70 SSB/109 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/109 Da) compared to those with wild-type genotype (0.83 ± 0.79 SSB/109 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. © 2007 Oxford University Press.
2007
28
3
657
664
Vodicka P.; Stetina R.; Polakova V.; Tulupova E.; Naccarati A.; Vodickova L.; Kumar R.; Hanova M.; Pardini B.; Slyskova J.; Musak L.; De Palma G.; Soucek P.; Hemminki K.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1765145
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