In the present study, four tagging SNPs and two more well studied polymorphisms (Intron 4 VNTR and Glu298Asp) the NOS3 gene were investigated to unravel the potential modifier effect of NOS3 gene on the progression of CKD in ADPKD.
The distribution of C/T alleIes is significantly different between rapid and slow ADPKD progressors leading to the conclusion that the T allele of the Glu298Asp polymorphism of NOS3 gene is associated with earlier progression to ESRD in ADPKD patients.
The endothelial nitric oxide synthase Glu298Asp and Asp29Asp genotypes were significantly more frequent in rapid progressors (9.6% (7/73) Asp/Asp, 39.7% (29/73) Asp/Glu, 50.7% (37/73) Glu/Glu) and in ADPKD group with ESRF between 40-63 years (11.3% (16/142) Asp/Asp, 41.5% (59/142) Asp/Glu, 47.2% (67/142) Glu/Glu) in comparison with slow progressors (8.8% (8/91) Asp/Asp, 24.2% (22/91) Asp/Glu, 67.0% (61/91) Glu/Glu) and with control group (8% Asp/Asp, 32% Asp/Glu, 60% Glu/Glu) (Chi-square test, p<0.05).
Previously, a glutamic acid to aspartic acid polymorphism at residue 298 (E/D298) of the endothelial nitric oxide synthase (eNOS) gene ENOS was associated with disease severity in males with ADPKD.