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

K. C. Barnes, L. Caraballo, M. Muñoz, A. Zambelli-Weiner, E. Ehrlich, M. Burki, S. Jimenez, R. A. Mathias, M. L. Stockton, P. Deindl, L. Mendoza, G. K. Hershey, R. Nickel, M. Wills-Karp

Research output: Contribution to journalArticle

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)736-744
Number of pages9
JournalClinical and Experimental Allergy
Volume34
Issue number5
DOIs
StatePublished - May 1 2004

Keywords

  • Association
  • Asthma
  • Atopy
  • Complement component 5 receptor 1 (C5R1)
  • Single-nucleotide polymorphism (SNP)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this

    Barnes, K. C., Caraballo, L., Muñoz, M., Zambelli-Weiner, A., Ehrlich, E., Burki, M., Jimenez, S., Mathias, R. A., Stockton, M. L., Deindl, P., Mendoza, L., Hershey, G. K., Nickel, R., & Wills-Karp, M. (2004). 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. Clinical and Experimental Allergy, 34(5), 736-744. https://doi.org/10.1111/j.1365-2222.2004.1942.x