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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Acknowledgements
We thank all the families and volunteers who graciously participated in this study. We are especially grateful to Dr Kathryn Held, Ms Sharon Patterson, Caitlin Dorer, and Kimberly Donnelly for fieldwork, and to Drs Paul Levett, Raana Naidu, and Harold Watson for facilitating the Barbados study. We thank Robert Munford for helpful discussions and Bo Zhang, Melba Muñoz, and Pat Oldewurtel for technical assistance. This work was supported by National Institutes of Health (NIH) Grants U01 HL66583 and HL67736, and an Allergy and Asthma Foundation of America Young Investigator Award. KCB was supported in part by the Mary Beryl Patch Turnbull Scholar Program.
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Barnes, K., Grant, A., Baltadzhieva, D. et al. Variants in the gene encoding C3 are associated with asthma and related phenotypes among African Caribbean families. Genes Immun 7, 27–35 (2006). https://doi.org/10.1038/sj.gene.6364267
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DOI: https://doi.org/10.1038/sj.gene.6364267
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