Effect of genetic polymorphisms of MnSOD and MPO on the relationship between PAH exposure and oxidative DNA damage

Abstract

To investigate the effect of genetic polymorphisms on the oxidative damage caused by PAH exposure, we measured urinary 1-hydroxypyrene (1-OHP) and 8-hydroxydeoxyguanosine (8-OHdG) levels to determine exposure and oxidative injury in university students. After examining myeloperoxidase (MPO) and manganese superoxide dismutase (MnSOD) genotypes by PCR and RFLP, we evaluated the effects of these polymorphisms on the relationship between the urinary levels of 1-OHP and 8-OHdG. No significant relation was observed between log 1-OHP and 8-OHdG concentrations in the whole study group (p = 0.182), or between urinary 8-OHdG levels and polymorphisms of MnSOD or MPO (p = 0.539 and 0.993, respectively). However, significant differences of regression coefficient were found for the relation between urinary log 1-OHP and urinary 8-OHdG concentrations in the presence of different MnSOD or MPO genotypes by multiple regression after controlling for age, sex, body mass index, cotinine, and smoking. In those with the MnSOD Val/Ala or Ala/Ala genotypes this regression coefficient was 1.480 (p = 0.040), whereas for the MnSOD Val/Val genotype it was 0.088 (p = 0.859). The higher regression coefficient was obtained for the subject group with the MnSOD Val/Ala or Ala/Ala genotype in combination with the MPO G/G genotype (p = 0.012). We suggest that the oxidative injury caused by PAH exposure is modulated by genetic polymorphisms such as MnSOD and MPO. © 2005 Elsevier B.V. All rights reserved.