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
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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. / 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.
in: CLIN EXP ALLERGY, Jahrgang 34, Nr. 5, 01.05.2004, S. 736-44.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - 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
AU - Barnes, K C
AU - Caraballo, L
AU - Muñoz, M
AU - Zambelli-Weiner, A
AU - Ehrlich, E
AU - Burki, M
AU - Jimenez, S
AU - Mathias, R A
AU - Stockton, M L
AU - Deindl, P
AU - Mendoza, L
AU - Hershey, G K
AU - Nickel, R
AU - Wills-Karp, M
PY - 2004/5/1
Y1 - 2004/5/1
N2 - 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.
AB - 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.
KW - African Continental Ancestry Group
KW - Asthma
KW - Barbados
KW - Base Sequence
KW - Child
KW - Child, Preschool
KW - Chromosomes, Human, Pair 19
KW - Cohort Studies
KW - European Continental Ancestry Group
KW - Female
KW - Gene Expression
KW - Gene Frequency
KW - Germany
KW - Humans
KW - Hypersensitivity
KW - Infant
KW - Infant, Newborn
KW - Male
KW - Membrane Proteins
KW - Molecular Sequence Data
KW - Point Mutation
KW - Promoter Regions, Genetic
KW - Receptors, Complement
KW - Transfection
KW - U937 Cells
KW - United States
U2 - 10.1111/j.1365-2222.2004.1942.x
DO - 10.1111/j.1365-2222.2004.1942.x
M3 - SCORING: Journal article
C2 - 15144465
VL - 34
SP - 736
EP - 744
JO - CLIN EXP ALLERGY
JF - CLIN EXP ALLERGY
SN - 0954-7894
IS - 5
ER -