Association of the human bradykinin B2 receptor gene with chronic renal failure.

Introduction: The kallikrein-kinin system plays an important role in blood pressure homeostasis and renal sodium regulation, and some studies have reported that the kinins have a protective effect against hypertension and the development of renal disease. The B2-bradykinin receptor (B2R) mediates the majority of physiological actions of bradykinin. We investigated the effect of the C181-->T polymorphism in exon 2 of the B2R gene in patients with end-stage renal disease (ESRD).

Methods: This study involved 790 patients with ESRD and 510 healthy controls. All participants were genotyped for the B2R C181-->T polymorphism by PCR followed by digestion of a PCR product with TaqI restriction endonuclease. DNA fragments were separated by agarose gel electrophoresis. Genotype and allele frequencies were compared between the groups. All calculations were performed using SPSS 5.0 for Windows.

Results: B2R genotype distribution in patients and controls was in accordance with Hardy-Weinberg equilibrium. The frequency of the T allele was higher in ESRD patients than in controls. The significant difference was observed in the age at onset of renal disease; for patients with the T allele the mean age at onset was 36.8 years, compared with 52.4 years for those carrying only the C allele (p<0.001). The frequencies of the T allele and carrier genotypes were not associated with gender, presence of hypertension, or underlying kidney disease.

Conclusion: Our results suggest that the B2R polymorphism has a potential role in the earlier development of chronic renal failure in susceptible individuals. We did not confirm the previously published reports that the B2R gene polymorphism has a protective role in the development of ESRD.