Variants in the gene encoding C3 are associated with asthma and related phenotypes among African Caribbean families

K. C. Barnes, A. V. Grant, D. Baltadzhieva, S. Zhang, T. Berg, L. Shao, A. Zambelli-Weiner, W. Anderson, A. Nelsen, S. Pillai, D. P. Yarnall, K. Dienger, R. G. Ingersoll, Alan F Scott, Daniele Daniele Fallin, Rasika Mathias, Terri L Beaty, J. G N Garcia, Marsha Wills-Karp

Research output: Contribution to journalArticle

Abstract

Proinflammatory and immunoregulatory products from C3 play a major role in phagocytosis, respiratory burst, and airways inflammation. C3 is critical in adaptive immunity; studies in mice deficient in C3 demonstrate that features of asthma are significantly attenuated in the absence of C3. To test the hypothesis that the C3 gene on chromosome 19p13.3-p13.2 contains variants associated with asthma and related phenotypes, we genotyped 25 single nucleotide polymorphism (SNP) markers distributed at intervals of ∼1.9 kb within the C3 gene in 852 African Caribbean subjects from 125 nuclear and extended pedigrees. We used the multiallelic test in the family-based association test program to examine sliding windows comprised of 2-6 SNPs. A five-SNP window between markers rs10402876 and rs366510 provided strongest evidence for linkage in the presence of linkage disequilibrium for asthma, high log[total IgE], and high log[IL-13]/[log[IFN-γ] in terms of global P-values (P = 0.00027, 0.00013, and 0.003, respectively). A three-SNP haplotype GGC for the first three of these markers showed best overall significance for the three phenotypes (P = 0.003, 0.007, 0.018, respectively) considering haplotype-specific tests. Taken together, these results implicate the C3 gene as a priority candidate controlling risk for asthma and allergic disease in this population of African descent.

Original languageEnglish (US)
Pages (from-to)27-35
Number of pages9
JournalGenes and Immunity
Volume7
Issue number1
DOIs
StatePublished - Jan 2006

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Single Nucleotide Polymorphism
Asthma
Phenotype
Haplotypes
Genes
Respiratory Burst
Interleukin-13
Linkage Disequilibrium
Adaptive Immunity
Pedigree
Phagocytosis
Immunoglobulin E
Chromosomes
Inflammation
Population

Keywords

  • Asthma
  • C3
  • Haplotype
  • IL-13
  • INF-γ
  • Total IgE

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Variants in the gene encoding C3 are associated with asthma and related phenotypes among African Caribbean families. / Barnes, K. C.; Grant, A. V.; Baltadzhieva, D.; Zhang, S.; Berg, T.; Shao, L.; Zambelli-Weiner, A.; Anderson, W.; Nelsen, A.; Pillai, S.; Yarnall, D. P.; Dienger, K.; Ingersoll, R. G.; Scott, Alan F; Fallin, Daniele Daniele; Mathias, Rasika; Beaty, Terri L; Garcia, J. G N; Wills-Karp, Marsha.

In: Genes and Immunity, Vol. 7, No. 1, 01.2006, p. 27-35.

Research output: Contribution to journalArticle

Barnes, KC, Grant, AV, Baltadzhieva, D, Zhang, S, Berg, T, Shao, L, Zambelli-Weiner, A, Anderson, W, Nelsen, A, Pillai, S, Yarnall, DP, Dienger, K, Ingersoll, RG, Scott, AF, Fallin, DD, Mathias, R, Beaty, TL, Garcia, JGN & Wills-Karp, M 2006, 'Variants in the gene encoding C3 are associated with asthma and related phenotypes among African Caribbean families', Genes and Immunity, vol. 7, no. 1, pp. 27-35. https://doi.org/10.1038/sj.gene.6364267
Barnes, K. C. ; Grant, A. V. ; Baltadzhieva, D. ; Zhang, S. ; Berg, T. ; Shao, L. ; Zambelli-Weiner, A. ; Anderson, W. ; Nelsen, A. ; Pillai, S. ; Yarnall, D. P. ; Dienger, K. ; Ingersoll, R. G. ; Scott, Alan F ; Fallin, Daniele Daniele ; Mathias, Rasika ; Beaty, Terri L ; Garcia, J. G N ; Wills-Karp, Marsha. / Variants in the gene encoding C3 are associated with asthma and related phenotypes among African Caribbean families. In: Genes and Immunity. 2006 ; Vol. 7, No. 1. pp. 27-35.
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abstract = "Proinflammatory and immunoregulatory products from C3 play a major role in phagocytosis, respiratory burst, and airways inflammation. C3 is critical in adaptive immunity; studies in mice deficient in C3 demonstrate that features of asthma are significantly attenuated in the absence of C3. To test the hypothesis that the C3 gene on chromosome 19p13.3-p13.2 contains variants associated with asthma and related phenotypes, we genotyped 25 single nucleotide polymorphism (SNP) markers distributed at intervals of ∼1.9 kb within the C3 gene in 852 African Caribbean subjects from 125 nuclear and extended pedigrees. We used the multiallelic test in the family-based association test program to examine sliding windows comprised of 2-6 SNPs. A five-SNP window between markers rs10402876 and rs366510 provided strongest evidence for linkage in the presence of linkage disequilibrium for asthma, high log[total IgE], and high log[IL-13]/[log[IFN-γ] in terms of global P-values (P = 0.00027, 0.00013, and 0.003, respectively). A three-SNP haplotype GGC for the first three of these markers showed best overall significance for the three phenotypes (P = 0.003, 0.007, 0.018, respectively) considering haplotype-specific tests. Taken together, these results implicate the C3 gene as a priority candidate controlling risk for asthma and allergic disease in this population of African descent.",
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AU - Berg, T.

AU - Shao, L.

AU - Zambelli-Weiner, A.

AU - Anderson, W.

AU - Nelsen, A.

AU - Pillai, S.

AU - Yarnall, D. P.

AU - Dienger, K.

AU - Ingersoll, R. G.

AU - Scott, Alan F

AU - Fallin, Daniele Daniele

AU - Mathias, Rasika

AU - Beaty, Terri L

AU - Garcia, J. G N

AU - Wills-Karp, Marsha

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N2 - Proinflammatory and immunoregulatory products from C3 play a major role in phagocytosis, respiratory burst, and airways inflammation. C3 is critical in adaptive immunity; studies in mice deficient in C3 demonstrate that features of asthma are significantly attenuated in the absence of C3. To test the hypothesis that the C3 gene on chromosome 19p13.3-p13.2 contains variants associated with asthma and related phenotypes, we genotyped 25 single nucleotide polymorphism (SNP) markers distributed at intervals of ∼1.9 kb within the C3 gene in 852 African Caribbean subjects from 125 nuclear and extended pedigrees. We used the multiallelic test in the family-based association test program to examine sliding windows comprised of 2-6 SNPs. A five-SNP window between markers rs10402876 and rs366510 provided strongest evidence for linkage in the presence of linkage disequilibrium for asthma, high log[total IgE], and high log[IL-13]/[log[IFN-γ] in terms of global P-values (P = 0.00027, 0.00013, and 0.003, respectively). A three-SNP haplotype GGC for the first three of these markers showed best overall significance for the three phenotypes (P = 0.003, 0.007, 0.018, respectively) considering haplotype-specific tests. Taken together, these results implicate the C3 gene as a priority candidate controlling risk for asthma and allergic disease in this population of African descent.

AB - Proinflammatory and immunoregulatory products from C3 play a major role in phagocytosis, respiratory burst, and airways inflammation. C3 is critical in adaptive immunity; studies in mice deficient in C3 demonstrate that features of asthma are significantly attenuated in the absence of C3. To test the hypothesis that the C3 gene on chromosome 19p13.3-p13.2 contains variants associated with asthma and related phenotypes, we genotyped 25 single nucleotide polymorphism (SNP) markers distributed at intervals of ∼1.9 kb within the C3 gene in 852 African Caribbean subjects from 125 nuclear and extended pedigrees. We used the multiallelic test in the family-based association test program to examine sliding windows comprised of 2-6 SNPs. A five-SNP window between markers rs10402876 and rs366510 provided strongest evidence for linkage in the presence of linkage disequilibrium for asthma, high log[total IgE], and high log[IL-13]/[log[IFN-γ] in terms of global P-values (P = 0.00027, 0.00013, and 0.003, respectively). A three-SNP haplotype GGC for the first three of these markers showed best overall significance for the three phenotypes (P = 0.003, 0.007, 0.018, respectively) considering haplotype-specific tests. Taken together, these results implicate the C3 gene as a priority candidate controlling risk for asthma and allergic disease in this population of African descent.

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KW - INF-γ

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