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.

中文翻译：

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编码C3的基因变异与非洲加勒比海家庭中的哮喘和相关表型有关。

C3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对于适应性免疫至关重要。对缺乏C3的小鼠的研究表明，在没有C3的情况下，哮喘的特征会明显减弱。为了检验19p13.3-p13.2染色体上的C3基因包含与哮喘和相关表型有关的变异的假说，我们对852个非洲人的C3基因内以大约1.9 kb的间隔分布的25个单核苷酸多态性（SNP）标记进行了基因分型。来自125个核谱系和扩展谱系的加勒比海学科。我们在基于家庭的关联测试程序中使用了多等位基因测试，以检查由2-6个SNP组成的滑动窗口。标记rs10402876和rs366510之间的5个SNP窗口为哮喘，高log [total IgE]和高log [IL-13] / [log [IFN-γ]的连锁不平衡存在时的连锁提供了最有力的证据。全局P值（分别为P = 0.00027、0.00013和0.003）。考虑到单倍型特异性测试，前三个标记的三单核苷酸多态性GGC对这三个表型（分别为P = 0.003、0.007、0.018）表现出最佳的总体意义。综上所述，这些结果表明C3基因是控制该非洲人后裔哮喘和过敏性疾病风险的优先候选对象。考虑到单倍型特异性测试，前三个标记的三单核苷酸多态性GGC对这三个表型（分别为P = 0.003、0.007、0.018）表现出最佳的总体意义。综上所述，这些结果表明C3基因是控制该非洲人后裔哮喘和过敏性疾病风险的优先候选对象。考虑到单倍型特异性测试，前三个标记的三单核苷酸多态性GGC对这三个表型（分别为P = 0.003、0.007、0.018）表现出最佳的总体意义。综上所述，这些结果表明C3基因是控制该非洲人后裔哮喘和过敏性疾病风险的优先候选对象。