Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease
Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease
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DOI：
10.1111/j.1398-9995.2009.02167.x
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发表时间：
2010-04-01
期刊：
影响因子：
12.4
通讯作者：
Sayers, I.
中科院分区：
文献类型：
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作者：
Beghe, B.;Hall, I. P.;Sayers, I.
研究背景：哮喘和慢性阻塞性肺疾病（COPD）是一种涉及遗传和环境因素相互作用的慢性呼吸系统疾病。白细胞介素-13（IL-13）已被认为在哮喘和COPD中起作用。我们调查了IL 13通路的单核苷酸多态性（SNP）是否可能与成人哮喘和COPD的易感性和严重程度有关。方法：对哮喘患者（n = 299）和COPD患者或健康吸烟者（n = 992）的IL 13通路基因IL 4、IL 13、IL 4 RA、IL 13 RA 1、IL 13 RA 2和STAT 6的12个SNP进行基因分型。使用基因型和等位基因模型评估哮喘严重程度、特应性表型和COPD易感性的遗传关联。结果：IL 13基因rs 1881457（-1512）、rs 1800925（-1111）和rs 20541（R130 Q）3个单核苷酸多态性与哮喘患者的特应性风险相关。IL 4 RA 1中的一个SNP [rs 1805010（I75 V）]与哮喘严重程度相关，并且几个IL 13 SNP显示临界显著性。IL 13基因多态性rs 1881457（-1512）和rs 1800925（-1111）与哮喘患者较好的FEV（1）和FEV（1）/FVC相关。在隐性模型中，IL 13 SNPs rs 2066960（内含子1）、rs 20541（R130 Q）和rs 1295685（外显子4）与COPD风险和较低的基线肺功能相关。结论：IL 13基因启动子区和编码区的单核苷酸多态性与特应性和哮喘的发生有关，IL 4 RA基因的单核苷酸多态性与特应性和哮喘的发生有关。我们还提供了初步的证据，IL 13编码区的SNPs可能是COPD易感性的意义。
P>Background:Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory diseases involving an interaction between genetic and environmental factors. Interleukin-13 (IL13) has been suggested to have a role in both asthma and COPD. We investigated whether single nucleotide polymorphisms (SNPs) in the IL13 pathway may contribute to the susceptibility and severity of asthma and COPD in adults.Methods:Twelve SNPs in IL13 pathway genes -IL4, IL13, IL4RA, IL13RA1, IL13RA2 and STAT6- were genotyped in subjects with asthma (n = 299) and in subjects with COPD or healthy smokers (n = 992). Genetic association was evaluated using genotype and allele models for asthma severity, atopy phenotypes and COPD susceptibility. Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV(1), FEV(1)/FVC).Results:In asthmatics, three IL13 SNPs - rs1881457(-1512), rs1800925(-1111) and rs20541(R130Q) - were associated with atopy risk. One SNP in IL4RA1 [rs1805010(I75V)] was associated with asthma severity, and several IL13 SNPs showed borderline significance. IL13 SNPs rs1881457(-1512) and rs1800925(-1111) were associated with better FEV(1) and FEV(1)/FVC in asthmatics. IL13 SNPs rs2066960(intron 1), rs20541(R130Q) and rs1295685(exon 4) were associated with COPD risk and lower baseline lung function in the recessive model. In females, but not in males, rs2250747 of the IL13RA1 gene was associated with COPD and lower FEV(1).Conclusion:These data suggest that IL13 SNPs (promoter and coding region) and, to a lesser extent, IL4RA SNPs may contribute to atopy and asthma. We also provide tentative evidence that IL13 SNPs in the coding region may be of significance in COPD susceptibility.