title: Characterization of two polymorphic sites in the human kinin B1 receptor gene: altered frequency of an allele in patients with a history of end-stage renal failure.
abstract: On the basis of the genomic structure of the human B1 receptor (B1R) for kinins, the presence of possible allelic polymorphisms of this gene 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 history of end-stage renal failure, because there is evidence for a nephroprotective action of the kallikrein-kinin system. An A1098-->G polymorphism has been identified in exon 3 in a minority of volunteer blood donors, and is located 35 nucleotides downstream from the stop codon and 14 nucleotides upstream from the polyadenylation signal. The frequency of the G allele is 4.4% in the control sample and not significantly 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 substitution (G-699-->C) in the putative promoter region. This polymorphism is significantly less frequent in the population of renal failure patients (prevalence of 20.6%) and determines an increased activity of the promoter function in constructions involving a reporter gene. The altered prevalence of this allele was also found in some etiologic subgroups of uremic patients. This study confirms the mapping of the B1R gene to 14q32. Other investigators have mapped the bradykinin B2 receptor (B2R) gene to a close site on human chromosome 14. A previously described B2R polymorphism (exon 2, C181-->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 significance for the preservation of renal function in diseased individuals.
authors.affiliation: Centre Hospitalier Universitaire de Québec, Centre de Recherche du Pavillon l'Hôtel-Dieu de Québec, Canada.
authors.forename: D R
authors.initials: DR
authors.lastname: Bachvarov
authors.forename: M
authors.initials: M
authors.lastname: Landry
authors.forename: I
authors.initials: I
authors.lastname: Pelletier
authors.forename: M
authors.initials: M
authors.lastname: Chevrette
authors.forename: C
authors.initials: C
authors.lastname: Betard
authors.forename: I
authors.initials: I
authors.lastname: Houde
authors.forename: J
authors.initials: J
authors.lastname: Bergeron
authors.forename: M
authors.initials: M
authors.lastname: Lebel
authors.forename: F
authors.initials: F
authors.lastname: Marceau
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D005787:Gene Frequency; D005819:Genetic Markers; D006801:Humans; D016234:Kallikrein-Kinin System / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018002:Receptors, Bradykinin / Q000235:genetics*; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D005819:Genetic Markers; D018002:Receptors, Bradykinin