Association between quantitative traits underlying asthma and the HLA-DRB1 locus in a family-based population sample
Association between quantitative traits underlying asthma and the HLA-DRB1 locus in a family-based population sample
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DOI：
10.1038/sj.ejhg.5200636
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发表时间：
2001-05-01
影响因子：
5.2
通讯作者：
Cookson, WOCM
中科院分区：
文献类型：
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作者：
Moffatt, MF;Schou, C;Cookson, WOCM
人类6号染色体包含MHC的区域已被确定为影响哮喘和变态反应（过敏）的几个全基因组搜索。MHC包含许多对先天免疫和特异性免疫有潜在影响的基因。作为剖析MHC对哮喘及其潜在定量表型影响的第一步，我们检查了来自澳大利亚乡村小镇Busselton 230个家庭的1004个个体的人群样本中的HLA-DRB1位点。该位点与血清总IgE浓度（log,）密切相关，占该性状σ(2)方差的4.0%（多等位基因检验，P=0.00001）。该位点还影响对常见过敏原的特异性IgE滴度(多等位基因试验，屋尘螨过敏原Der p I的特异性IgE滴度为2.8% sigma (2), p =0.0013；3.0% sigma(2)对于Der p II， p =0.0007；猫过敏原feld1的sigma(2)为2.1%，P=0.014)。没有发现哮喘的分类表型，或外周血嗜酸性粒细胞计数和支气管高反应性的数量特征的关联。传播不平衡测试排除了基因混杂作为假阳性结果的原因。结果表明，HLA-DRB1等位基因调节血清总IgE浓度和IgE对过敏原的反应，但不能解释先前观察到的哮喘与MHC的联系。
The region of human chromosome 6 containing the MHC has been identified as influencing asthma and atopy (allergy) by several genome-wide searches. The MHC contains many genes with potential effects on innate and specific immunity. As a first step in dissecting MHC influences on asthma and its underlying quantitative phenotypes, we have examined the HLA-DRB1 locus in a population sample consisting of 1004 individuals from 230 families from the rural Australian town of Busselton. The locus was strongly associated with the (log,) total serum IgE concentration, accounting for 4.0% of the sigma (2) (variance) in that trait (multiallelic test, P=0.00001). The locus also influenced specific IgE titres to common allergens (multi-allelic tests, 2.8% sigma (2) for the house dust mite allergen Der p I, P=0.0013; 3.0% of sigma (2) for Der p II, P=0.0007; and 2.1% of sigma (2) for the cat allergen Fel d I, P=0.014). No associations were found to the categorical phenotype of asthma, or to the quantitative traits of peripheral blood eosinophil counts and bronchial hyper-responsiveness. Transmission disequilibrium tests excluded genetic admixture as a cause of false-positive findings. The results indicate that HLA-DRB1 alleles modulate the total serum IgE concentration and IgE responses to allergens, but do not account for the previous observations of linkage of asthma to the MHC.