Relationship Between β1-Adrenergic Receptor Polymorphisms and Cardiovascular Disease in Peritoneal Dialysis Patients

Abstract

Recent studies show that a common gain-of-function polymorphism of β1-adrenergic receptor (389 Gly→Arg) plays an important role in the pathogenesis of hypertension and heart failure in patients with normal renal function. We studied the relationship between β1-adrenergic receptor polymorphism and cardiovascular disease in peritoneal dialysis (PD) patients. We studied 189 new PD patients. The β 1-adrenergic receptor genotype was determined by polymerase chain reaction-restriction fragment length polymorphism assay. They were then prospectively followed for the development of cardiovascular events. All-cause mortality and duration of hospitalization were also recorded. There were 95 male cases. The mean age was 56.2 ± 14.8 years. Eighty-six (45.5%) patients were diabetic; 81 (42.9%) received beta-blocker therapy. Only one case was homozygous for the mutant CC genotype. The prevalence of GG, GC, and CC genotypes were 34.9%, 64.6%, and 0.5%, respectively. The genotype distribution was significantly different from that predicted by the assumption of Hardy-Weinberg equilibrium ( p < 0.0001). There was no difference in the prevalence of pre-existing cardiovascular disease between genotype groups. Actuarial patient survival was 80.2% and 85.1% at 24 months for the GG and GC/CC genotypes, respectively ( p = 0.53). Event-free survival was 63.6% and 71.5% at 24 months, respectively ( p = 0.26), and the duration of hospitalization was 15.9 ± 3.0 and 16.6 ± 2.3 days per year, respectively ( p = 0.8). The results remained similar when patients with and without beta-blocker treatment were separately analyzed. Our study demonstrates that the β 1-adrenergic receptor polymorphism is not related to cardiovascular disease in PD patients. Nevertheless, the low prevalence of mutant CC genotype in new PD patients suggests that PD patients represent a highly biased population.