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.
David K Simon, Tanya Simuni, Jordan Elm, Joanne Clark-Matott, Allison K Graebner, Liana Baker, Susan R Dunlop, Marina Emborg, Cornelia Kamp, John C Morgan, G Webster Ross, Saloni Sharma, Bernard Ravina
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