Chan I H S, Tang N L S, Leung T F, Huang W, Lam Y Y O, Li C Y, Wong C K, Wong G W K, Lam C W K
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Allergy. 2008 Aug;63(8):1031-9. doi: 10.1111/j.1398-9995.2008.01639.x.
Asthma is a complex disease resulting from interactions between multiple genes and environmental factors. Study of gene-gene interactions could provide insight into the pathophysiology of asthma.
We investigated the interactions among 18 single-nucleotide polymorphisms in eight candidate genes for plasma total immunoglobulin E (IgE) concentration and peripheral blood (PB) eosinophil count in 298 Chinese asthmatic children and 175 controls. Generalized multifactor dimensionality reduction and generalized linear model were used to analyze gene-gene interactions for the quantitative traits.
A significant interaction was found between R130Q in IL13 and I50V in IL4RA for plasma total IgE concentration, with a cross-validation (CV) consistency of nine of 10 and a prediction error of 41.1% (P = 0.013). Plasma total IgE concentration was significantly higher in the high-risk than the low-risk groups (P < 0.0001). For PB eosinophil count, significant interaction was found between C-431T in TARC and RsaI_in2 in FCERIB, with a CV consistency of nine of 10 and a prediction error of 40.2% (P = 0.009). PB eosinophil count was significantly higher in the high-risk group than the low-risk groups (P < 0.0001). Generalized linear model also revealed significant gene-gene interaction for the above two endophenotypes with P = 0.013 for plasma total IgE concentration and P = 0.029 for PB eosinophil count respectively.
Our data suggest significant interactions between IL13 and IL4RA for plasma total IgE concentration, and this is the first report to show significant interaction between TARC and FCERIB for PB eosinophil count in Chinese asthmatic children.
哮喘是一种由多种基因与环境因素相互作用导致的复杂疾病。基因-基因相互作用的研究有助于深入了解哮喘的病理生理学。
我们在298名中国哮喘儿童和175名对照中，研究了8个候选基因中18个单核苷酸多态性之间对于血浆总免疫球蛋白E（IgE）浓度和外周血（PB）嗜酸性粒细胞计数的相互作用。采用广义多因素降维和广义线性模型分析数量性状的基因-基因相互作用。
对于血浆总IgE浓度，发现白细胞介素13（IL13）中的R130Q与白细胞介素4受体A（IL4RA）中的I50V之间存在显著相互作用，十次交叉验证（CV）中有九次一致，预测误差为41.1%（P = 0.013）。高风险组的血浆总IgE浓度显著高于低风险组（P < 0.0001）。对于PB嗜酸性粒细胞计数，发现胸腺活化调节趋化因子（TARC）中的C-431T与高亲和力IgE受体β链（FCERIB）中的RsaI_in2之间存在显著相互作用，十次交叉验证中有九次一致，预测误差为40.2%（P = 0.009）。高风险组的PB嗜酸性粒细胞计数显著高于低风险组（P < 0.0001）。广义线性模型也显示上述两种内表型存在显著的基因-基因相互作用，血浆总IgE浓度的P值为0.013，PB嗜酸性粒细胞计数的P值为0.029。
我们的数据表明IL13与IL4RA之间对于血浆总IgE浓度存在显著相互作用，这是首次报道在中国哮喘儿童中TARC与FCERIB之间对于PB嗜酸性粒细胞计数存在显著相互作用。
