Human Evaluation of the Glu298Asp polymorphism in NOS3 gene and its relationship with onset age of ESRD in Iranian patients suffering from ADPKD

One of the most striking features in autosomal dominant polycystic kidney disease (ADPKD) is the difference at onset age of end-stage renal disease (ESRD). Modifier genes may play a role in this phenotypic variability. The mutated nitric oxide synthase 3 gene (NOS3), have a modifier effect on the severity of ADPKD by impairment of NOS3 activity and decreasing of renal vascular nitric oxide production and, subsequently, reduced kidney function. In order to test this hypothesis, we investigated the relationship between Glu298Asp polymorphism in exon 7 of this gene and ESRD in ADPKD patients refered from Shahid Labbafi Nedjad Hospital in Tehran. The polymorphism was examined by PCR, followed by RFLP (with MboI) in three groups of ADPKD with ESRD; ADPKD without ESRD patients and normal individual as the cases, case-controls and controls, respectively. The frequencies of GG, GT, and TT genotypes in cases were 66.7%, 33.3% and 0%, in case-controls were 78.6%, 19%, 2.4%, and in controls were 64.3%, 35.7% and 0%, respectively. Our findings revealed that there was no significant difference in the genotype frequency of NOS3 gene in ADPKD patients (p=0.311).The age of onset of ESRD in ADPKD patients, harbouring the T allele of this polymorphism, was two years lower than G/G patients, but this difference was not significant (p =0.641). In conclusion, our results suggest that there is no evidence of relationship between Glu298Asp polymorphism and onset age of ESRD in Iranian ADPKD patients.