Base excision repair gene polymorphisms are associated with inflammation in patients undergoing chronic hemodialysis

Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, China.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 07/2012; 424(3):611-5. DOI: 10.1016/j.bbrc.2012.06.161
Source: PubMed


Chronic inflammation may increase the risk of mortality for patients undergoing hemodialysis, while enhanced oxidative stress and DNA oxidative damage are involved in the inflammatory response. The purpose of this study was to examine the associations between inflammation and polymorphisms in the base excision repair (BER) system, which protects against oxidative DNA damage, among hemodialysis patients. Data were analyzed from 167 hemodialysis patients and 66 healthy controls. All subjects were evaluated for the expression of inflammatory cytokines (IL-1β and IL-6) and genotyped for two BER genes, including hOGG1 c.977C>G, MUTYH c.972G>C and AluYb8MUTYH. The results showed that the hemodialysis patients had significantly higher levels of IL-1β and IL-6 than the healthy controls. In the healthy controls, no patterns of association were observed between the hOGG1 c.977C>G or MUTYH c.972G>C genotypes and IL-1β or IL-6 levels; however, patients with the MUTYH c.972G/G genotype presented higher levels of IL-1β than those with the C/C genotype. The AluYb8MUTYH genotype was strongly associated with increased IL-1β levels among controls and increased IL-1β and IL-6 levels among hemodialysis patients. Additionally, the synergetic effect of these variations of the BER genes on the levels of IL-1β and IL-6 was investigated. The combinations of the AluYb8MUTYH genotype with the hOGG1 c.977 C>G or MUTYH c.972 G>C genotypes were associated with the IL-1β and IL-6 levels in hemodialysis patients. This is the first report showing an association between BER genetic polymorphisms and the inflammatory state during hemodialysis; this association might be mediated by impaired anti-oxidant defense mechanisms.

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    ABSTRACT: In recent years, the understanding of how DNA repair contributes to the development of innate and acquired immunity has emerged. The DNA damage incurred during the inflammatory response triggers the activation of DNA repair pathways, which are required for host-cell survival. Here, we reviewed current understanding of the mechanism by which DNA repair contributes to protection against the oxidized DNA damage generated during infectious and inflammatory diseases and its involvement in innate and adaptive immunity. We discussed the functional role of DNA repair enzymes in the immune activation and the relevance of these processes to: transcriptional regulation of cytokines and other genes involved in the inflammatory response; V(D)J recombination; class-switch recombination (CSR); and somatic hypermutation (SHM). These three last processes of DNA damage repair are required for effective humoral adaptive immunity, creating genetic diversity in developing T and B cells. Furthermore, viral replication is also dependent on host DNA repair mechanisms. Therefore, the elucidation of the pathways of DNA damage and its repair that activate innate and adaptive immunity will be important for a better understanding of the immune and inflammatory disorders and developing new therapeutic interventions for treatment of these diseases and for improving their outcome. Copyright © 2014 Elsevier B.V. All rights reserved.
    Mutation Research/Reviews in Mutation Research 11/2014; 763. DOI:10.1016/j.mrrev.2014.11.004 · 6.21 Impact Factor

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