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

被引:29
|
作者
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, MD
Mathias, RA
Beaty, TH
Garcia, JGN
Wills-Karp, M
机构
[1] Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA
[2] Johns Hopkins Univ, Sch Med, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD USA
[3] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA
[4] GlaxoSmithKline Inc, Res Triangle Pk, NC USA
[5] Childrens Hosp, Med Ctr, Childrens Hosp, Res Fdn,Div Immunobiol, Cincinnati, OH USA
[6] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA
[7] Natl Human Genome Res Inst, Inherited Dis Res Branch, NIH, Baltimore, MD USA
[8] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD USA
关键词
asthma; C3; total IgE; IL-13; INF-gamma; haplotype;
D O I
10.1038/sj.gene.6364267
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 similar to 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.
引用
收藏
页码:27 / 35
页数:9
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