TGFβ1 allele association with asthma severity
TGFβ1 allele association with asthma severity
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DOI：
10.1007/s00439-001-0617-y
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发表时间：
2001-12-01
期刊：
影响因子：
5.3
通讯作者：
Barnes, PJ
中科院分区：
文献类型：
--
作者：
Pulleyn, LJ;Newton, R;Barnes, PJ
转化生长因子β 1（TGF β 1）是一种多功能细胞因子，参与促炎和抗炎途径，并在几种细胞类型中表达。上皮下纤维化是哮喘气道重塑的主要特征之一，并且在严重患者中增加。TGF β 1参与纤维化，包括细胞外基质蛋白的沉积。与轻度哮喘患者相比，重度哮喘患者嗜酸性粒细胞中TGF β 1 mRNA水平升高。因此，TGF β 1是一个有希望的候选基因，有助于哮喘的严重程度。在重度哮喘组、轻度哮喘组和对照组中，根据激素使用情况和肺功能对启动子区和信号肽区的4个多态性（C-509 T、72 insC、T869 C和G915 C）进行基因分型。C-509 T基因型频率在两组间存在显著差异（P=0.016），主要归因于重度组中-509T等位基因纯合性的相对频率高于轻度组和对照组。-509T纯合的个体在72 C、869 C和915 G等位基因的其他变异位点也是纯合的（单倍型1）。T等位基因产生了一个假定的YY 1转录因子结合位点，但在体外没有检测到YY 1和T等位基因的DNA序列之间的结合。在这项研究中，我们发现单倍型I上的-509T变异是TGF β 1对哮喘严重程度贡献的最具信息性的标志物。
Transforming growth factor beta1 (TGFbeta1) is a multifunctional cytokine involved in pro- and anti-inflammatory pathways and is expressed in several cell types. Subepithelial fibrosis is one of the principle features of airway remodelling in asthma and is increased in severe patients. TGFbeta1 is implicated in fibrosis, including the deposition of extracellular matrix proteins. TGFbeta1 mRNA levels in eosinophils are increased in severe asthmatics relative to mild asthmatics. Therefore, TGFbeta1 is a promising candidate gene for contributing to asthma severity. Four polymorphisms located in the promoter region and signal peptide (C-509T, 72insC, T869C and G915C) were genotyped in groups of severe asthmatic, mild asthmatic or control individuals defined by steroid usage and pulmonary function. Significant difrerences (P=0.016) were found between the groups for the genotype frequencies at C-509T, attributable mainly to a greater relative frequency of homozygosity for the -509T allele in the severe group compared to the mild and control groups. Individuals homozygous for -509T were also homozygous at the other variant sites for the 72C, 869C and 915G alleles (haplotype 1). The T allele creates a putative YY1 transcription factor binding site, but binding between YY1 and the DNA sequence of the T allele was not detected in vitro. In this study, we show that the -509T variant on haplotype I is the most informative marker of the TGFbeta1 contribution to asthma severity.