تعيين اثرات انالاپريل و لوزارتان بر روي آسيب DNA سلولي در بيماران پيوند كليه اي با پلي مورفيسم هاي سيستم رنين - آنژيوتانسين

The Effects of Enalapril and Losartan on DNA Damage in Renal Transplant Recipients with Regarding to Renin-Angiotensin System Polymorphisms

Background and Objectives: Oxidative injury of DNA and lipids may be supervised by renin-angiotensin system (RAS). In the study the effect of losartan (L) and/or enalapril (E) on reduction of DNA damage was evaluated regarding to renin-angiotensin system polymorphisms. Materials and Methods: After determination of genotypes of the angiotensin converting enzyme (ACE I/D), angiotensinogen (AGT M235T) and angiotensin II type 1 receptor (ATR1 A1166C) by polymerase chain reaction, 64 renal transplant recipients randomly allocated to one of the four groups: first (13 patients) and second (20 patients) groups were treated with E (E+: 10mg/d) and L (L+: 50 mg/d) alone respectively. The third group (13 patients) as positive control received E+L (E+L+: 10mg/d + 50 mg/d) and the forth group (22 cases) received no medication as negative control (E-L-). The subjects were followed for 8 weeks. After 2 weeks washout period, E group changed to L and vice versa as cross-over design. They were followed for another 8 weeks. Before and after 2 months treatment, we checked the serum 8-OHdG and Malondialdehyde (MDA) as biomarkers of DNA damage and lipid peroxidation respectively. Results: Serum 8-OHdG levels were significantly decreased in the E+L+ and L+ groups (6.07±1.1 ng/ml to 3.6±0.58 ng/ml, P=0.000; 5.30±0.86 ng/ml to 3.6±0.47 ng/ml, P=0.001 respectively). 8-OHdG level was not decreased significantly in E+ group (6±1.19 ng/ml to 4.7±1.39 ng/ml, P=0.07) and E-L- group (5.30±0.84 to 5.6±0.88 ng/ml, P=0.11). Patients with DD genotype of ACE and CC genotype of ATR1 had higher serum 8-OHdG levels at the basline (P=0.02, P=0.002 respectively). Only TT genotype of AGT had the most antioxidative role regarding to kind of above treatment regimens (P=0.01). We found a remarkable correlation between MDA and DNA damage levels before and after intervention (r=0.48, P=0.000; r=0.35, P=0.006). Conclusion: Although serum 8-OHdG level is higher in DD and CC genotypes of ACE and ATR1 polymorphisms; the protective effects of L+ and E+L+ on DNA breaks are surprising regarding to the RAS genotypes. TT genotype of AGT had important role in prevention of DNA break regarding to kind of treatment