CHARACTERIZATION OF 2 POLYMORPHIC SITES IN THE HUMAN KININ B-1 RECEPTOR GENE - ALTERED FREQUENCY OF AN ALLELE IN PATIENTS WITH A HISTORY OFEND-STAGE RENAL-FAILURE

On the basis of the genomic structure of the human B-1 receptor (B1R) for kinins, the presence of possible allelic polymorphisms of this gen e was investigated using restriction fragment-length polymorphism and single-strand conformation polymorphism. The frequencies of the found alleles were determined in healthy volunteers and in patients with a h istory of end-stage renal failure, because there is evidence for a nep hroprotective action of the kallikrein-kinin system. An A(1098) --> G polymorphism has been identified in exon 3 in a minority of volunteer blood donors, and is located 35 nucleotides downstream from the stop c odon and 14 nucleotides upstream from the polyadenylation signal. The frequency of the G allele is 4.4% in the control sample and not signif icantly altered in patients with a history of end-stage renal failure. A second and more frequent polymorphism (18.1% of the alleles in the control group, prevalence of 33.3%) consists of a single base substitu tion (G(-699)-->C) in the putative promoter region. This polymorphism is significantly less frequent in the population of renal failure pati ents (prevalence of 20.6%) and determines an increased activity of the promoter function in constructions involving a reporter gene. The alt ered prevalence of this allele was also found in some etiologic subgro ups of uremic patients. This study confirms the mapping of the B1R gen e to 14q32. Other investigators have mapped the bradykinin B, receptor (B2R) gene to a close site on human chromosome 14. A previously descr ibed B2R polymorphism (exon 2, C-181 --> T) had an allele frequency of 9.7% in the control sample and appears to be clinically neutral. The polymorphism of the B1R promoter may be a marker of prognostic signifi cance for the preservation of renal function in diseased individuals.