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