Prevention of DNA damage in renal transplantation by losartan and enalapril: the role of renin-angiotensin system polymorphisms.

BACKGROUND: In this study the effect of losartan and enalapril on the reduction of DNA damage was evaluated in regard to renin-angiotensin system (RAS) polymorphisms. METHODS: After determination of genotypes of RAS polymorphism by PCR, 64 renal transplant recipients were randomly allocated to one of four groups: the first and second groups were treated with E (E+: 10 mg/day) and L (L+: 50 mg/day) alone, respectively. The third group received E+L (E+L+: 10 + 50 mg/day), and the forth group received no medication (E-L-). The subjects were followed for 8 weeks. After a 2-week washout period, the E group changed to L and vice versa as a cross-over design. They were followed for another 8 weeks. Before and after treatment, we checked 8-OHdG and malondialdehyde (MDA) as biomarkers of DNA damage and lipid peroxidation, respectively. RESULTS: 8-OHdG levels were significantly decreased after treatment in the E+L+ and L+ groups (P < 0.001, P = 0.001, respectively). Only the TT genotype of AGT had the most antioxidative role regarding the treatment (P = 0.01). We found a remarkable correlation between MDA and DNA damage levels before and after intervention (r = 0.48, P < 0.001; r = 0.35, P = 0.006). CONCLUSION: The protective effects of L+ and E+L+ on DNA breaks are surprising regarding the RAS polymorphisms.

Renin-angiotensin system polymorphisms and renal graft function in renal transplant recipients.

OBJECTIVE: To analyze the role of 3 polymorphisms of the renin-angiotensin system (RAS) in renal transplant recipients (RTRs) and correlate them with graft function. METHODS: The present study was performed in the Drug Applied Research Center, Tabriz Medical University, Tabriz, Iran from September 2003 to December 2005 on 108 RTRs (66 males and 42 females, with a mean age of 37.34 +/- 4.97 years) with stable allograft function (creatinine < or =2.2 mg/dl). Following the DNA extraction from the blood leukocytes, the genotypes of the angiotensin converting enzyme (ACE I/D), angiotensinogen (ANG M235T), and angiotensin II type 1 receptor (ATR1 A1166C) were determined by polymerase chain reaction. The magnitude of clearance of creatinine (ClCr) in the setting of each of the above RAS polymorphisms was determined. The ClCr was measured by modification of diet in renal disease formula. Values were expressed as mean +/- SD; p< or =0.05 was considered to indicate statistical significance. RESULTS: There was no association of each genotype of the RAS alone with ClCr, serum urea, cyclosporine through level and the degree of urinary protein excretion rate. However, patients with the DD genotype of angiotensin converting enzyme + CC genotype of angiotensin II type I receptor polymorphisms had lower ClCr (p=0.05) and a higher urinary protein excretion rate (p=0.03). Other combination genotypes of RAS had no effect on allograft function. Interestingly, the percent of hypertensive patients in the C allele (70%) was more than the A allele (30%) of ATR1 polymorphism (p=0.04). CONCLUSION: Although none of the single gene polymorphisms of the RAS affected renal allograft function, combinations of these genotypes were associated with the outcome of allograft function.

Enalapril and losartan affect lipid peroxidation in renal transplant recipients with renin-angiotensin system polymorphisms.

OBJECTIVES: In this study, the effect of enalapril (E) and/or losartan (L) on lipid peroxidation (LPO) is studied in renal transplant recipients (RTRs) with regard to polymorphisms of renin-angiotensin system (RAS). DESIGN 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 PCR, sixty-four RTRs recruited to four groups randomly: first (13 patients) and second (20 patients) groups were treated with enalapril (E(+): 10 mg/day) and losartan (L(+): 50 mg/day) alone for 2 months, respectively. After 2 weeks as washout period, E group changed to L and vice versa as a cross-over design and they were treated for another 2 months. The third group (13 patients) as positive control received enalapril+losartan (E(+)L(+): 10 mg/day+50 mg/day) for 16 weeks, and the forth group (18 patients) as negative control received no medication (E(-)L(-)). Malondialdehyde (MDA) as LPO marker was measured before and after treatment. In this study, P<0.05 was considered significant. RESULTS: After 2 months of treatment, MDA level significantly decreased in all of the groups except the E(-)L(-). MDA level in pre- vs. post-intervention for the E(+)L(+), E(+), L(+) and E(-)L(-) groups were as follows: 5.81+/-2.13 nmol/mL vs. 1.61+/-0.80 nmol/mL (P=0.001), 5.10+/-2.05 nmol/mL vs. 1.68+/-1.01 nmol/mL (P=0.003), 5.20+/-1.61 nmol/mL vs. 1.22+/-0.27 nmol/mL (P=0.000) and 5.27+/-2.12 nmol/mL vs. 5.07+/-2.03 nmol/mL (P=0.52), respectively. Also, the same results were found in the end of 16th week. Although patients with DD genotype of ACE had higher MDA (P=0.01) levels, RAS polymorphisms could not predict the antioxidative response rate to the drugs (P>0.05). CONCLUSIONS: E and/or L reduce MDA regardless of the RAS genotypes.

Cardiovascular disease risk factors in patients with confirmed cardiovascular disease.

OBJECTIVE: To assess the magnitude of the problem of cardiovascular risk factors in hospitalized patients, and to establish cardiovascular disease (CVD) risk factor profiles. METHODS: The study included 476 confirmed CVD patients selected by a multi stage stratified cluster random sampling technique in Tabriz Heart Center (Shaheed Madani Hospital), Tabriz, Iran from February 2004 to May 2005. After obtaining demographic information and performing physical examination, biochemical parameters were measured. Data was analyzed using the Statistical Package for Social Science version 10.05, where p value of <0.05 was considered significant. RESULTS: Obesity was the most common abnormality (93.5%) followed by diabetes mellitus (58.4%), low high-density lipoprotein cholesterol (HDL-c) (45.4%), low physical activity (41.6%), high total cholesterol (40.1%), high triglyceride (37.2%), high low-density lipoprotein cholesterol (30.7%), diastolic hypertension (28.4%), high systolic blood pressure (24.8%) and smoking (20%). Of the total number of patients, 93% had one risk factors for CVD, 43% had 2, 16% had 3, and 5% had 4 risk factors. The prevalence of lipid disorders in females was more than males except for low HDL-c (p<0.05). Between lipid profiles, only TG showed a correlation between age (p<0.05). It was noticed that obesity accompanied by lipid profile abnormalities as low serum levels of HDL-c and high level of TG, TC, and LDL-c were more seen in obese patients (p<0.05). CONCLUSION: This study revealed a high prevalence of risk factors in CVD patients; thus, urgent lifestyle modification is recommended.