Effect of human OGG1 1245C -> G gene polymorphism on 8-hydroxy-2 '-deoxyguanosine levels of leukocyte DNA among patients undergoing chronic hemodialysis

Citation
Dc. Tarng et al., Effect of human OGG1 1245C -> G gene polymorphism on 8-hydroxy-2 '-deoxyguanosine levels of leukocyte DNA among patients undergoing chronic hemodialysis, J AM S NEPH, 12(11), 2001, pp. 2338-2347
Citations number
47
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
ISSN journal
10466673 → ACNP
Volume
12
Issue
11
Year of publication
2001
Pages
2338 - 2347
Database
ISI
SICI code
1046-6673(200111)12:11<2338:EOHO1->2.0.ZU;2-Y
Abstract
The effects of the human OGG1 gene (hOGG1) 1245C -->G polymorphism on the 8 -hydroxy-2'-deoxyguanosine (8-OHdG) contents of peripheral leukocyte DNA we re investigated among chronic hemodialysis patients. First, the hOGG1 1245C -->G transversion was assessed, by using a PCR-restriction fragment length polymorphism method, among 210 hemodialysis patients and 156 healthy indiv iduals. Second, the 8-OHdG contents in leukocyte DNA were measured, by usin g an HPLC-electrochemical detection method, for 112 hemodialysis patients a nd 112 age-, gender-, and genotype-matched healthy control subjects. The th ree genotypes (as dummy variables) and age, gender, dialysis duration, dial yzer membrane type, blood antioxidant levels, and iron parameters were used as independent variables and the natural logarithm of the leukocyte 8-OHdG concentration was used as a dependent variable in a forward, stepwise, mul tiple-regression model. The results demonstrated that the allelic frequency of hOGG1 1245G was 64.1% among 210 hemodialysis patients and 62.2% in the whole control population. The genotypic frequencies (CC/CG/GG ratio, 10%/51 .9%/38.1%) for the hemodialysis patients did not differ significantly from those (16.7%/42.3%/41.0%) for the control subjects (P > 0.05, chi (2) test) . The mean leukocyte 8-OHdG levels for the patients were significantly high er than those for the healthy control subjects (P < 0.001). Leukocyte 8-OHd G levels were further increased among patients with the 1245GG genotype, co mpared with patients with the 1245CG or CC genotype (P < 0.001, ANOVA), but levels were similar among healthy control subjects irrespective of the hOG G1 gene polymorphism. It was also observed that patients who underwent dial ysis with cellulose membranes exhibited significantly higher leukocyte 8-OH dG levels than did patients who underwent dialysis with polymethylmethacryl ate, polysulfone, or vitamin E-bonded membranes (P < 0.001, ANOVA), The mul tivariate regression analysis revealed that hOGG1 1245C<right arrow>G polym orphism and dialysis membrane type were the two independent predictors of 8 -OHdG contents in leukocyte DNA from hemodialysis patients. This study demo nstrated that the extent of oxidative DNA damage among chronic hemodialysis patients not only is influenced by overproduction of reactive oxygen speci es resulting from leukocyte contacts with complement-activating membranes a nd by impaired antioxidant defense mechanisms but also is genetically deter mined.