Centre for Molecular Biology and Neuroscience, Institute of Microbiology, University of Oslo, Norway.
Mech Ageing Dev. 2011 Aug;132(8-9):449-58. doi: 10.1016/j.mad.2011.08.002. Epub 2011 Aug 22.
To test the hypothesis that single nucleotide polymorphisms (SNPs) in DNA repair genes are associated with cognitive performance during normal aging, the relationship between SNPs in selected exons in DNA base excision repair (BER) genes and cognitive performance was examined in 712 healthy Norwegian individuals aged 20-75 years. SNPs examined included PolB(Pro242Arg), hOGG1(Ser326Cys), MutYH (Met22Val), MutYH(His324Gln), APE1(Gln51His), APE1(Glu148Asp), XRCC1(Lys298Asn), XRCC1(Arg7Leu), NEIL1(Asp252Asn), and NEIL2(Arg257Leu). XRCC1(Arg7Leu) and PolB(Pro242Arg) were characterized by single nucleotide variations (≤0.1% homozygote SNPs). hOGG1(Ser326Cys) (Ser/Cys 40.8%/Cys/Cys 5.7%), MutYH(His324Gln) (His/Gln37%/Gln/Gln 6.0%) and APE1(Glu148Asp) (Glu/Asp 51.3%/Asp/Asp 23.0%) were characterized by higher SNP frequencies. MutYH(Met22Val), APE1(Gln51His) and NEIL2(Arg257Leu) occurred at intermediate SNP frequencies of 11.5, 7.6 and 5.3%, respectively. Interestingly, hOGG1(Ser326Cys) and APE1(Gln51His) had genotype by age interactions with general cognitive function, reasoning, control and speed of processing in cross-sectional analysis and a significant effect on longitudinal decline. Dispersed association effects involving MutYH(His324Gln), MutYH(Met22Val), PolB(Pro242Arg) and NEIL2(Arg257Leu) were also detected when APOE or CHRNA4, were included in the statistical model, a result consistent with proposed involvement of the latter markers in human cognitive decline and/or function. In summary, the results support the notion that polymorphisms in BER genes modulate cognitive performance in healthy elderly individuals.
为了验证假设，即 DNA 修复基因中的单核苷酸多态性（SNPs）与正常衰老过程中的认知表现有关，研究人员在 712 名年龄在 20-75 岁的健康挪威个体中，检查了 DNA 碱基切除修复（BER）基因中选定外显子中的 SNPs 与认知表现之间的关系。检查的 SNPs 包括 PolB（Pro242Arg）、hOGG1（Ser326Cys）、MutYH（Met22Val）、MutYH（His324Gln）、APE1（Gln51His）、APE1（Glu148Asp）、XRCC1（Lys298Asn）、XRCC1（Arg7Leu）、NEIL1（Asp252Asn）和 NEIL2（Arg257Leu）。XRCC1（Arg7Leu）和 PolB（Pro242Arg）的特征是单核苷酸变异（≤0.1%纯合子 SNPs）。hOGG1（Ser326Cys）（Ser/Cys 为 40.8%/Cys/Cys 为 5.7%）、MutYH（His324Gln）（His/Gln 为 37%/Gln/Gln 为 6.0%）和 APE1（Glu148Asp）（Glu/Asp 为 51.3%/Asp/Asp 为 23.0%）的 SNP 频率较高。MutYH（Met22Val）、APE1（Gln51His）和 NEIL2（Arg257Leu）的 SNP 频率分别为 11.5%、7.6%和 5.3%，处于中等水平。有趣的是，在横断面分析中，hOGG1（Ser326Cys）和 APE1（Gln51His）的基因型与年龄存在与一般认知功能、推理、控制和处理速度的相互作用，并且对纵向下降有显著影响。当 APOE 或 CHRNA4 纳入统计模型时，还检测到涉及 MutYH（His324Gln）、MutYH（Met22Val）、PolB（Pro242Arg）和 NEIL2（Arg257Leu）的分散关联效应，这与后一种标记物在人类认知能力下降和/或功能中的作用一致。总之，这些结果支持这样一种观点，即 BER 基因中的多态性调节健康老年人的认知表现。
