Endothelial Nitric Oxide Synthase and Angiotensin II Type 1 Receptor Gene Polymorphisms Can Influence Chronic Inflammatory State in Renal Transplant Patients

Abstract

Serum C-reactive protein (CRP) is a sensitive indicator of inflammation. Because increasing evidence shows the effect of endothelial nitric oxide synthase (eNOS) and the renin–angiotensin system on inflammation, we studied the association among chronic inflammation, chronic rejection, and gene polymorphisms of angiotensin II type 1 receptor (ATR1) and eNOS in renal transplant patients. Methods Data from 80 male and 35 female renal transplant patients (mean follow-up, 60.6 ± 22.2 months) were analyzed. Patients were grouped according to posttransplant CRP levels: group 1 patients ( n = 46) had normal CRP levels (CRP <10 mg/L); group 2 had intermittent ( n = 26), and group 3 had persistently elevated ( n = 43) CRP levels. eNOS and ATR1 gene polymorphisms of the groups and the impact of posttransplant CRP response on development of chronic rejection and graft failure were analyzed. The bb allele of the eNOS gene was found in 74% of the patients, whereas 62% had AA allele of ATR1. Results Patients in group 1 had a significantly lower incidence of chronic rejection and graft failure when compared with patients in groups 2 and 3 ( P = .05 and P = .02 respectively). The bb allele of the eNOS gene predominated in group 1 ( P = .02); presence of non-AA allele of ATR1 1166 gene was found less frequently in group 3 ( P = .01). Conclusions The presence of the bb allele of the eNOS and non-AA allele of ATR1 1166 gene is associated with an anti-inflammatory state and may predict renal outcome in transplant patients.