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中国儿童哮喘与血浆总免疫球蛋白E浓度的基因-基因相互作用

Gene-gene interactions for asthma and plasma total IgE concentration in Chinese children.

作者信息

Chan Iris H S, Leung Ting F, Tang Nelson L S, Li Chung Y, Sung Ying M, Wong Gary W K, Wong Chun K, Lam Christopher W K

机构信息

Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.

出版信息

J Allergy Clin Immunol. 2006 Jan;117(1):127-33. doi: 10.1016/j.jaci.2005.09.031. Epub 2005 Dec 2.

Abstract

BACKGROUND

Asthma is a complex disease resulting from interactions between multiple genes and environmental factors. Study of gene-gene interactions could provide insight into asthma pathophysiology.

OBJECTIVE

We investigated the interaction among 12 different loci in 8 candidate genes and asthma and increased plasma total IgE concentrations in 240 Chinese asthmatic subjects and 140 control subjects.

METHODS

Genotyping was performed by means of RFLP analysis. Multifactor dimensionality reduction and logistic regression were used to analyze gene-gene interactions.

RESULTS

A significant interaction was found between R130Q in the IL-13 gene (IL13) and I50V in the IL-4 receptor alpha gene (IL4RA) on the risk of asthma, with a cross-validation consistency of 10 of 10 and a prediction error of 33.7% (P = .014). The odds ratio of the high-risk to low-risk group was 2.6 (95% CI, 1.4-5.0; P = .004). For increased plasma total IgE concentration, the best 2-locus model consisted of R130Q in IL13 and C-431T in the thymus and activation-regulated chemokine gene (TARC). This model showed a maximum cross-validation consistency of 10 and a minimum prediction error of 36.1% (P = .022). The odds ratio of the high-risk to low-risk group was 3.9 (95% CI, 2.0-7.7; P = .0001). Logistic regression revealed significant interactions between IL13 and IL4RA for asthma (P = .042) and IL13 and TARC for increased total IgE concentration (P = .012).

CONCLUSIONS

Our data suggest significant interactions between IL13 and IL4RA for asthma and IL13 and TARC for increased plasma total IgE concentrations in Chinese children.

摘要

背景

哮喘是一种由多个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。

目的

我们在240名中国哮喘患者和140名对照受试者中,研究了8个候选基因中12个不同位点之间的相互作用与哮喘以及血浆总IgE浓度升高之间的关系。

方法

采用限制性片段长度多态性分析进行基因分型。运用多因素降维和逻辑回归分析基因-基因相互作用。

结果

在哮喘风险方面,白细胞介素13基因(IL13)中的R130Q与白细胞介素4受体α基因(IL4RA)中的I50V之间存在显著相互作用,交叉验证一致性为10/10,预测误差为33.7%(P = 0.014)。高风险组与低风险组的比值比为2.6(95%可信区间,1.4 - 5.0;P = 0.004)。对于血浆总IgE浓度升高,最佳的两位点模型由IL13中的R130Q和胸腺与活化调节趋化因子基因(TARC)中的C - 431T组成。该模型显示最大交叉验证一致性为10,最小预测误差为36.1%(P = 0.022)。高风险组与低风险组的比值比为3.9(95%可信区间,2.0 - 7.7;P = 0.0001)。逻辑回归显示,IL13与IL4RA在哮喘方面存在显著相互作用(P = 0.042),IL13与TARC在总IgE浓度升高方面存在显著相互作用(P = 0.012)。

结论

我们的数据表明,在中国儿童中,IL13与IL4RA在哮喘方面以及IL13与TARC在血浆总IgE浓度升高方面存在显著相互作用。

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