title: A novel promoter polymorphism in the gene encoding complement component 5 receptor 1 on chromosome 19q13.3 is not associated with asthma and atopy in three independent populations.
abstract: BACKGROUND
  The inflammatory functions of complement component 5 (C5) are mediated by its receptor, C5R1, which is expressed on bronchial, epithelial, vascular endothelial and smooth muscle cells. A susceptibility locus for murine allergen-induced airway hyper-responsiveness was identified in a region syntenic to human chromosome 19q13, where linkage to asthma has been demonstrated and where the gene encoding C5R1 is localized.
  
  
  OBJECTIVE
  The aim of this study was to screen for novel polymorphisms in the C5R1 gene and to determine whether any identified polymorphisms are associated with asthma and/or atopy and whether they are functional.
  
  
  METHODS
  Single-nucleotide polymorphism (SNP) detection in the gene encoding C5R1 was performed by direct sequencing. Genotyping was performed in three populations characterized for asthma and/or atopy: (1) 823 German children from The Multicenter Allergy Study; (2) 146 individuals from Tangier Island, Virginia, a Caucasian isolate; and (3) asthma case-parent trios selected from 134 families (N=783) in Barbados. Functional studies were performed to evaluate differences between the wild-type and the variant alleles.
  
  
  RESULTS
  We identified a novel SNP in the promoter region of C5R1 at position -245 (T/C). Frequency of the -245C allele was similar in the German (31.5%) and Tangier Island (36.3%) populations, but higher in the Afro-Caribbean population (53.0%; P=0.0039 to <0.0001). We observed no significant associations between the -245 polymorphism and asthma or atopy phenotypes. Upon examination of the functional consequences of the -245T/C polymorphism, we did not observe any change in promoter activity.
  
  
  CONCLUSIONS
  This new marker may provide a valuable tool to assess the risk for C5a-associated disorders, but it does not appear to be associated with asthma and/or atopy.
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland 21224, USA. kbarnes@jhmi.edu
authors.forename: K C
authors.initials: KC
authors.lastname: Barnes
authors.forename: L
authors.initials: L
authors.lastname: Caraballo
authors.forename: M
authors.initials: M
authors.lastname: Muñoz
authors.forename: A
authors.initials: A
authors.lastname: Zambelli-Weiner
authors.forename: E
authors.initials: E
authors.lastname: Ehrlich
authors.forename: M
authors.initials: M
authors.lastname: Burki
authors.forename: S
authors.initials: S
authors.lastname: Jimenez
authors.forename: R A
authors.initials: RA
authors.lastname: Mathias
authors.forename: M L
authors.initials: ML
authors.lastname: Stockton
authors.forename: P
authors.initials: P
authors.lastname: Deindl
authors.forename: L
authors.initials: L
authors.lastname: Mendoza
authors.forename: G K
authors.initials: GK
authors.lastname: Hershey
authors.forename: R
authors.initials: R
authors.lastname: Nickel
authors.forename: M
authors.initials: M
authors.lastname: Wills-Karp
mesh_terms: D001249:Asthma / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D001460:Barbados; D001483:Base Sequence; D044383:Black People; D002648:Child; D002675:Child, Preschool; D002888:Chromosomes, Human, Pair 19; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005858:Germany; D006801:Humans; D006967:Hypersensitivity / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000235:genetics*; D014162:Transfection / Q000379:methods; D020298:U937 Cells; D014481:United States; D044465:White People; D001741:Black or African American
chemical_list: C488033:C5AR1 protein, human; D008565:Membrane Proteins; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement