AGER -429T/C is associated with an increased lung disease severity in cystic fibrosis.
AGER -429T/C is associated with an increased lung disease severity in cystic fibrosis.
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DOI：
10.1371/journal.pone.0041913
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
French C F Modifier Gene Study Investigators
中科院分区：
文献类型：
--
作者：
Beucher J;Boëlle PY;Busson PF;Muselet-Charlier C;Clement A;Corvol H;French C F Modifier Gene Study Investigators
囊性纤维化（CF）的临床过程在携带相同CFTR突变的患者之间变化，表明修饰基因的参与。我们评估了来自法国CF基因修饰物研究的CF患者中肺部疾病严重程度与AGER-429 T/C变异体的相关性，AGER-429 T/C编码一种促炎蛋白--β 1。我们分析了967例p.Phe508del纯合子CF患者的肺功能。FEV 1分析为根据年龄、身高和死亡率调整的CF特定百分位数。对AGER-429 T/C多态性进行基因分型，并通过测量荧光素酶活性来体外评估其功能。AGER-429次要等位基因（C）与肺功能较差相关（p = 0.03）。 在体外，与用AGER-429 T等位基因转染的细胞相比，用AGER-429 C转染的细胞中的启动子活性更高（在BEAS-2B细胞中p=0.016）。 AGER可能是CF肺部疾病严重程度的调节基因，并可能是CF气道炎症的一个有趣的生物标志物。功能性启动子AGER-429 C变体与增加的HSP 70表达相关，其可导致增加的肺部炎症和更严重的肺部疾病。
The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV1 was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.
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DOI：
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发表时间：
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影响因子：
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作者：
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