The Influence of G-Protein β3-Subunit Gene and Endothelial Nitric Oxide Synthase Gene in Exon 7 Polymorphisms on Progression of Autosomal Dominant Polycystic Kidney Disease

Background: A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD). The variability cannot be fully explained by the genetic heterogeneity of the disease. We examined the influence of G-protein β3-subunit C825T polymorphism and endothelial nitric oxide synthase Glu298Asp polymorphism on the progression of ADPKD towards end stage renal failure (ESRF). Methods: 306 ADPKD patients (pts) were analyzed; 261 pts (136 males, 125 females) with ESRF, with subgroup of 73 pts (44 males, 29 females) with ESRF before 45 years (rapid progressors), 46 pts (20 males, 26 females) with ESRF later than in 63 years (slow progressors) and 45 ADPKD pts (17 males, 28 females) in mean age 51 years with serum creatinine under 110 µmol L (slow progressors) and 100 genetically unrelated healthy Czech subjects. DNA samples from collected blood were genotyped for G-protein β3-subunit C825T genotype in exon 10 and for endothelial nitric oxide synthase Glu298Asp genotype in exon 7. Results: The G-protein β3-subunit C825T genotype exhibited no significant differences among the groups of slow progressors (6.6% (6 91) TT, 54.9% (50 91) CT, 38.8% (35 91) CC), rapid progressors (9.6% (7 73) TT, 46.6% (34 73) CT, 43.8% (32 73) CC), ADPKD group with ESRF between 40-63 years (9.2% (13 142) TT, 50% (71 142) CT, 40.8% (58 142) CC) and control group (12% TT, 44% CT, 44% CC). When comparing the ages of ESRF of all patients with ESRF, we did not find significant differences in the ages: males TT-51.7 ± 8.8 years, CT-51.9 ± 10.3 years, CC-49.7 ± 10.2 years and females TT-56 ± 9.9 years, CT-53.2 ± 8.5 years, CC-53.9 ± 8.7 years. 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). Comparing the ages of ESRF of all patients with ESRF, we did not find significant differences in the ages in males with Asp Asp-54.9 ± 10.4 years, Asp Glu-50.2 ± 9.4 years, Glu Glu-51.0 ± 10.4 years. We found out in homozygous Asp Asp females significantly earlier onset of ESRF (49.2 ± 5.6 years) in comparison with heterozygo