title: Variants in the gene encoding C3 are associated with asthma and related phenotypes among African Caribbean families.
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 approximately 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-gamma] 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.
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. kbarnes@jhmi.edu
authors.forename: K C
authors.initials: KC
authors.lastname: Barnes
authors.forename: A V
authors.initials: AV
authors.lastname: Grant
authors.forename: D
authors.initials: D
authors.lastname: Baltadzhieva
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: T
authors.initials: T
authors.lastname: Berg
authors.forename: L
authors.initials: L
authors.lastname: Shao
authors.forename: A
authors.initials: A
authors.lastname: Zambelli-Weiner
authors.forename: W
authors.initials: W
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Nelsen
authors.forename: S
authors.initials: S
authors.lastname: Pillai
authors.forename: D P
authors.initials: DP
authors.lastname: Yarnall
authors.forename: K
authors.initials: K
authors.lastname: Dienger
authors.forename: R G
authors.initials: RG
authors.lastname: Ingersoll
authors.forename: A F
authors.initials: AF
authors.lastname: Scott
authors.forename: M D
authors.initials: MD
authors.lastname: Fallin
authors.forename: R A
authors.initials: RA
authors.lastname: Mathias
authors.forename: T H
authors.initials: TH
authors.lastname: Beaty
authors.forename: J G N
authors.initials: JG
authors.lastname: Garcia
authors.forename: M
authors.initials: M
authors.lastname: Wills-Karp
mesh_terms: D001249:Asthma / Q000235:genetics*; D001460:Barbados / Q000208:ethnology; D044383:Black People / Q000208:ethnology; D017691:Caribbean Region / Q000208:ethnology; D003176:Complement C3 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: C038245:C3 protein, human; D003176:Complement C3