Increased frequency of G-protein β3-subunit 825 T allele in dialyzed patients with type 2 diabetes

Abstract

A polymorphism (C825T) in exon 10 of the gene encoding the beta 3 subunit of heterotrimeric G proteins (GN beta 3) has recently been described, and the T allele was found to be associated with late-onset hypertension. Because hypertension is a known risk factor for the development of clinically manifest progressive renal disease, we examined the C825T polymorphism in older hemodialysis patients suffering from nondiabetic renal disease or type 2 diabetes with presumed diabetic nephropathy, respectively, and in older healthy controls. Genotyping was performed by polymerase chain reaction, followed by restriction enzyme analysis. The study showed that the frequency of the T allele in the nondiabetic patients on dialysis (0.232) was significantly (P < 0.03) lower than in older healthy controls (0.293). In contrast, the frequency was significantly (P < 0.02) higher in older patients with type 2 diabetes on dialysis. No significant change in T-allele frequency was noted in older patients with type 2 diabetes without microangiopathy (0.286). The odds ratios for patients with type 2 diabetes on dialysis versus nondiabetic patients on dialysis were 3.24 (1.3 to 7.9, P < 0.00079) for TT/CC and 1.82 (1.07 to 3.09, P < 0.02) for CT/CC. The respective odds ratios for patients with type 2 diabetes on dialysis versus controls were 2.05 (1.07 to 3.9, P < 0.028) for CT/CC and 1.216 (0.79 to 1.87; P < 0.37) for CT/CC. The data do not support a role of the hypertension-associated T allele in the genesis of dialysis-dependent end-stage renal failure in general, but are compatible with a specific role of the T allele in the development or progression of diabetic nephropathy.