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

Abstract

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.

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

“…In the current paper and previous work, we have shown the relation between polymorphisms of the XRCC1, PARP1, APEX1, LIG1, and LIG3 genes and AD risk [23]. In light of these data and the results of other research teams, it can be stated that the processes associated with DNA damage are important in the formation and development of neurodegenerative diseases including AD [24,25].…”

Relationship between TBX20 gene polymorphism and congenital heart disease

“…Previous studies have shown that TBX20 polymorphisms are closely related to the occurrence and development of CHD in children Kwiatkowski et al, 2015;Lin et al, 2015;Monroy-Muñoz et al, 2015), results of this study were in concordance with those of previous studies. TBX20 SNP loci that have been reported thus far include: rs6950175 and rs3999941.…”

“…The evaluation of single nucleotide polymorphisms (SNP) is a key approach to explore and identify genetic predispositions to a certain condition (Lin et al, 2015), particularly for polygenic disease research (Kwiatkowski et al, 2015;Knopp et al, 2015). Through the study of SNPs in predisposing genes, the relationship between the gene and the disease can be clarified, which is of significant value for disease diagnosis, treatment, and prognosis.…”

Associations between DNA Damage, DNA Base Excision Repair Gene Variability and Alzheimer's Disease Risk

“…Other polymorphic variants largely increased the risk of AD, except for T/T of the APEX c.444T>G polymorphism; A/A of PARP1 c.2285T>C SNP, and G/A of XRCC1 c.580C>T, which exert a protective effect against AD. Results for the variants G/A of XRCC1 c.1196A>G and A/A of the PARP1 c.2285T>C polymorphism were consistent with those obtained in our previous studies [32]. Moreover, basal DNA damage was significantly higher in the C/T variant of XRCC1 c.1196A>G SNP carriers compared to other genotypes in AD patients, while T/T variant carriers of the same SNP (which demonstrated protective properties relative to AD in our previous study) exhibited increased DRE as compared to other polymorphic variants.…”