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 A F, Fallin M D, Mathias R A, Beaty T H, Garcia J G N, Wills-Karp M
Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Genes Immun. 2006 Jan;7(1):27-35. doi: 10.1038/sj.gene.6364267.
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.
补体C3产生的促炎和免疫调节产物在吞噬作用、呼吸爆发和气道炎症中起主要作用。C3在适应性免疫中至关重要；对C3缺陷小鼠的研究表明，在缺乏C3的情况下，哮喘特征会显著减轻。为了验证位于19号染色体p13.3 - p13.2上的C3基因包含与哮喘及相关表型相关的变异这一假设，我们对来自125个核心和扩展家系的852名非洲裔加勒比人进行基因分型，这些个体的C3基因内每隔约1.9 kb分布有25个单核苷酸多态性（SNP）标记。我们在基于家系的关联测试程序中使用多等位基因测试来检查由2 - 6个SNP组成的滑动窗口。在连锁不平衡存在的情况下，标记rs10402876和rs366510之间的一个五个SNP窗口，就哮喘、高log[总IgE]和高log[IL - 13]/[log[IFN - γ]]而言，在全局P值方面提供了最强的连锁证据（分别为P = 0.00027、0.00013和0.003）。考虑单倍型特异性测试，这三个标记中前三个标记的一个三个SNP单倍型GGC对这三种表型显示出最佳的总体显著性（分别为P = 0.003、0.007、0.018）。综上所述，这些结果表明C3基因是该非洲裔人群中控制哮喘和过敏性疾病风险的首要候选基因。
