Polymorphisms of STAT-6, STAT-4 and IFN-γ genes and the risk of asthma in Chinese population
Polymorphisms of STAT-6, STAT-4 and IFN-γ genes and the risk of asthma in Chinese population
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DOI：
10.1016/j.rmed.2007.04.006
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发表时间：
2007-09-01
影响因子：
4.3
通讯作者：
Zhang, Lu
中科院分区：
文献类型：
--
作者：
Li, Yafei;Wu, Bo;Zhang, Lu
背景：哮喘是一种多基因-基因、基因-环境相互作用的复杂疾病。基因-基因相互作用的研究有助于深入了解该病的病理生理机制。目的：方法：采用聚合酶链反应-单链构象多态性（PCR-SSCP）分析方法，对95名中国哮喘患者和95名正常对照者的STAT-6 G2964 A、STAT-4 T90089 C和IFN-γ T874 A三个候选基因的单核苷酸多态性及其相互作用进行研究。使用逻辑回归在显性和隐性遗传模型中检查基因型-表型关联。结果：哮喘组与对照组STAT-6基因G2964 A多态性分布差异无统计学意义。在显性模型中，STAT-4 T90089 C多态性与哮喘显著相关（p = 0.007）。对于IFN-γ T874 A，在显性模型（p = 0.004）和隐性模型（p = 0.006）中都发现了显著关联。STAT-6、STAT-4和IFN-γ在哮喘发病风险中存在显著的基因-基因交互作用。结论：STAT-4基因T90089 C和IFN-γ基因T874 A多态性可能是中国人群哮喘发病的遗传因素。此外，STAT-6 G2964 A、STAT-4 T90089 C和IFN-γ T874 A之间的显著相互作用可能增加个体的易感性并有助于哮喘的发病机制。(c)2007爱思唯尔有限公司保留所有权利。
Background: Asthma is a complex disease resulting from multiple gene-gene and gene-environment interactions. Study on gene-gene interactions could provide insight into the pathophysiologic mechanisms of the disease. Objectives: We investigated the single nucleotide polymorphisms and interactions among three different loci in three candidate genes (STAT-6 G2964A, STAT-4 T90089C and IFN-gamma T874A) in 95 Chinese asthmatic subjects and 95 matched controls to determine the possible associations with asthma.Methods: Genotyping of the gene polymorphisms was performed by means of PCR-SSCP analysis. Genotype-phenotype associations were examined in dominant and recessive genetic models using logistic regression. The method of multifactor dimensionality reduction was used to analyze gene-gene interactions.Results: No statistically significant difference was found in the distribution of the STAT-6 G2964A polymorphisms between asthmatic patients and controls in this case-control study. The STAT-4 T90089C polymorphisms were significantly associated with asthma in the dominant model (p = 0.007). As for the IFN-gamma T874A, the significant associations were found in both dominant model (p = 0.004) and recessive model (p = 0.006). A significant gene-gene interaction was found among STAT-6, STAT-4 and IFN-gamma on the risk of asthma. In the best 3-locus model, the odds ratio for the high-risk to the low-risk group was 6.9 (95% CI, 3.5-13.7; p < 0.0001).Conclusions: Our findings suggest that STAT-4 T90089C and IFN-gamma T874A polymorphisms might be the genetic factors for the risk of asthma in the Chinese population. In addition, the significant interactions among STAT-6 G2964A, STAT-4 T90089C and IFN-gamma T874A may increase an individual's susceptibility and contribute to the pathogenesis of asthma. (c) 2007 Elsevier Ltd. All rights reserved.