Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects
Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects
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DOI：
10.1093/carcin/bgl187
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发表时间：
2007-03-01
期刊：
影响因子：
4.7
通讯作者：
Hemminki, Kari
中科院分区：
文献类型：
--
作者：
Vodicka, Pavel;Stetina, Rudolf;Hemminki, Kari
我们研究了健康人群中 DNA 修复基因的多态性与修复由伽马射线照射和碱基氧化引起的 DNA 损伤的能力之间的关联。与野生型基因型个体（1.10 +/- 0.70 SSB/10(9) Da，P = 0.0006，Mann-Witney U 检验）相比，XRCC1 Arg399Gln 纯合变异基因型个体（0.45 +/- 0.47 SSB/10(9) Da）的辐射特异性 DNA 修复率显着降低。与野生型基因型个体（0.83 +/- 0.79 SSB/10(9) Da，P = 0.008，Mann-Witney U 检验）相比，hOGG1 Ser326Cys 纯合变异基因型个体（0.37 +/- 0.28 SSB/10(9) Da）修复氧化DNA损伤的能力显着降低。基因型组合的研究表明，XRCC1 Arg399Gln 和 APE1 Asn148Glu 多态性的变异等位基因数量的增加导致辐射特异性修复率显着下降（P = 0.008，Kruskal-Wallis 检验）。辐射特异性 DNA 修复率也随着 XRCC1 Arg399Gln 中变异等位基因数量的增加以及其他两个 XRCC1 多态性 Arg194Trp 和 Arg280His 的变异等位基因数量的增加而降低（分别为 P = 0.002 和 P = 0.005；Kruskal-Wallis 检验）。在二元组合中，hOGG1 Ser326Cys 和 APE1 Asn148Glu 多态性等位基因与修复 DNA 氧化损伤的能力显着下降相关（P = 0.018，Kruskal-Wallis 检验）。总之，XRCC1 Arg399Gln 和 hOGG1 Ser326Cys 多态性似乎分别对辐射特异性 DNA 修复能力和修复 DNA 氧化损伤的能力发挥主要调节作用。
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.