Single nucleotide polymorphisms in base-excision repair genes hOGG1, APE1 and XRCC1 do not alter risk of Alzheimer's disease

Parildar-Karpuzoglu, Hande; Doğru‐Abbasoğlu, Semra; Hanağası, Haşmet; Karadağ, Berrin; Gürvit, Hakan; Emre, Murat; Uysal, Müjdat

doi:10.1016/j.neulet.2008.07.047

Cited by 46 publications

(31 citation statements)

References 42 publications

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“…XRCC1 has no enzymatic activity but it acts as a scaffold for other proteins by interacting with many proteins involved in the BER pathway and single-strand break repair. A relation between the Arg194Trp polymorphism of the XRCC1 gene and an increased risk of AD in the Turkish population has been shown [45,46]. However, that same research team showed no correlation between the polymorphisms hOGG1 -C.977C>G, APE1 -Asp148Glu, and XRCC1 -Arg399Gln and AD.…”

Section: Discussionmentioning

confidence: 99%

Association between Single-Nucleotide Polymorphisms of the hOGG1,NEIL1,APEX1, FEN1,LIG1, and LIG3 Genes and Alzheimer's Disease Risk

Kwiatkowski

Czarny²,

Toma³

et al. 2016

Neuropsychobiology

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Background: One of the factors that contribute to Alzheimer's disease (AD) is the DNA damage caused by oxidative stress and inflammation that occurs in nerve cells. It has been suggested that the risk of AD may be associated with an age-dependent reduction of the DNA repair efficiency. Base excision repair (BER) is, among other things, a main repair system of oxidative DNA damage. One of the reasons for the reduced efficiency of this system may be single-nucleotide polymorphisms (SNP) of the genes encoding its proteins. Methods: DNA for genotyping was obtained from the peripheral blood of 281 patients and 150 controls. In the present study, we evaluated the impact of 8 polymorphisms of 6 BER genes on the AD risk. We analyzed the following SNP: c.-468T>G and c.444T>G of APEX1, c.*50C>T and c.*83A>C of LIG3, c.977C>G of OGG1, c.*283C>G of NEIL1, c.-441G>A of FEN1, and c.-7C>T of LIG1. Results: We showed that the LIG1 c.-7C>T A/A and LIG3 c.*83A>C A/C variants increased, while the APEX1 c.444T>G G/T, LIG1 c.-7C>T G/, LIG3 c.*83A>C C/C variants reduced, the AD risk. We also evaluated the relation between gene-gene interactions and the AD risk. We showed that combinations of certain BER gene variants such as c.977C>G×c.*50C>T CC/CT, c.444T>G×c.*50C>T GG/CT, c.-468T>G×c.*50C>T GG/CT, c.-441G>Ac.*50C>T×c.*50C>T GG/CT, c.*83A>C× c.*50C>T CT/AC, and c.-7C>T×c.*50C>T CT/GG can substantially positively modulate the risk of AD. Conclusions: In conclusion, we revealed that polymorphisms of BER genes may have a significant effect on the AD risk, and the presence of polymorphic variants may be an important marker for AD.

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Section: Discussionmentioning

confidence: 99%

Association between Single-Nucleotide Polymorphisms of the hOGG1,NEIL1,APEX1, FEN1,LIG1, and LIG3 Genes and Alzheimer's Disease Risk

Kwiatkowski

Czarny²,

Toma³

et al. 2016

Neuropsychobiology

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“…Some studies have shown that there is a correlation between age and the risk of pancreatic cancer [27]. Research conducted on 91 patients showed no correlation between the presence of the c.1196A>G polymorphism and AD in a Turkish population [28]. In some cases researchers have confirmed an association between this SNP and many varieties of cancer [29,30,31].…”

Section: Discussionmentioning

confidence: 99%

Variants of Base Excision Repair Genes MUTYH, PARP1 and XRCC1 in Alzheimer's Disease Risk

Kwiatkowski

Czarny²,

Gałecki³

et al. 2015

Neuropsychobiology

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Background: Many clinical studies have shown that oxidative stress pathways and the efficiency of the oxidative DNA damage base excision repair (BER) system are associated with the pathogenesis of Alzheimer's disease (AD). Reduced BER efficiency may result from polymorphisms of BER-related genes. In the present study, we examine whether single nucleotide polymorphisms (SNPs) of BER genes are associated with increased risk of AD. Methods: SNP genotyping was carried out on DNA isolated from peripheral blood mononuclear cells obtained from 120 patients with AD and 110 healthy volunteers. Samples were genotyped for the presence of BER-related SNPs, i.e. XRCC1-rs1799782, rs25487; MUTYH-rs3219489, and PARP1-rs1136410. Results: We found a positive association between AD risk and the presence of G/A genotype variant of the XRCC1 rs25487 polymorphism [odds ratio (OR) = 3.762, 95% CI: 1.793-7.891]. The presence of the A/A genotype of this polymorphism reduced the risk of AD (OR = 0.485, 95% CI: 0.271-0.870). In cases of the PARP1 gene rs1136410 polymorphism, we observed that the T/C variant increases (OR = 4.159, 95% CI: 1.978-8.745) while the T/T variant reduces risk (OR = 0.240, 95% CI: 0.114-0.556) of AD. Conclusions: We conclude that BER gene polymorphisms may play an important role in the etiology of AD. Diagnosing the presence or absence of particular genetic variants may be an important marker of AD. Further research on a larger population is needed. There is also a need to examine polymorphisms of other BER in the context of AD risk.

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“…Generally consistent with this earlier work, Davydov et al (34) reported that APE1 protein levels tended to be higher in mid-frontal cortex nuclear extracts of AD patients, and Marcon et al (134) observed more intense nuclear immunostaining of APE1 in the pathogenic regions of both sporadic and familial AD brains. Molecular epidemiology association studies, however, have indicated that the polymorphic variant of APE1 (D148E) as well as common SNPs in OGG1 and XRCC1 are not independent risk factors of AD (159). With regard to PD, one recent study involving 60 case subjects and 108 normal controls found that the D148E variant of APE1 had a positive association as a risk factor for the disease (59), although it was acknowledged by the authors that more extensive follow-up experiments are needed to validate this observation.…”

Section: Neuropathologymentioning

confidence: 99%

Human Apurinic/Apyrimidinic Endonuclease 1

2014

Antioxidants & Redox Signaling

224

221

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Significance: Human apurinic/apyrimidinic endonuclease 1 (APE1, also known as REF-1) was isolated based on its ability to cleave at AP sites in DNA or activate the DNA binding activity of certain transcription factors. We review herein topics related to this multi-functional DNA repair and stress-response protein. Recent Advances: APE1 displays homology to Escherichia coli exonuclease III and is a member of the divalent metal-dependent a/b fold-containing phosphoesterase superfamily of enzymes. APE1 has acquired distinct active site and loop elements that dictate substrate selectivity, and a unique N-terminus which at minimum imparts nuclear targeting and interaction specificity. Additional activities ascribed to APE1 include 3¢-5¢ exonuclease, 3¢-repair diesterase, nucleotide incision repair, damaged or site-specific RNA cleavage, and multiple transcription regulatory roles. Critical Issues: APE1 is essential for mouse embryogenesis and contributes to cell viability in a genetic background-dependent manner. Haploinsufficient APE1 +/ -mice exhibit reduced survival, increased cancer formation, and cellular/tissue hyper-sensitivity to oxidative stress, supporting the notion that impaired APE1 function associates with disease susceptibility. Although abnormal APE1 expression/localization has been seen in cancer and neuropathologies, and impaired-function variants have been described, a causal link between an APE1 defect and human disease remains elusive. Future Directions: Ongoing efforts aim at delineating the biological role(s) of the different APE1 activities, as well as the regulatory mechanisms for its intra-cellular distribution and participation in diverse molecular pathways. The determination of whether APE1 defects contribute to human disease, particularly pathologies that involve oxidative stress, and whether APE1 small-molecule regulators have clinical utility, is central to future investigations. Antioxid. Redox Signal. 20,

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Single nucleotide polymorphisms in base-excision repair genes hOGG1, APE1 and XRCC1 do not alter risk of Alzheimer's disease

Cited by 46 publications

References 42 publications

Association between Single-Nucleotide Polymorphisms of the <b><i>hOGG1,</i></b><b><i>NEIL1,</i></b><b><i>APEX1, FEN1,</i></b><b><i>LIG1,</i></b> and <b><i>LIG3</i></b> Genes and Alzheimer's Disease Risk

Association between Single-Nucleotide Polymorphisms of the <b><i>hOGG1,</i></b><b><i>NEIL1,</i></b><b><i>APEX1, FEN1,</i></b><b><i>LIG1,</i></b> and <b><i>LIG3</i></b> Genes and Alzheimer's Disease Risk

Variants of Base Excision Repair Genes <b><i>MUTYH</i></b>, <b><i>PARP1</i></b> and <b><i>XRCC1</i></b> in Alzheimer's Disease Risk

Human Apurinic/Apyrimidinic Endonuclease 1

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