Genetic Variations in Inflammatory Mediators Influence Lung Disease Progression in Cystic Fibrosis
Genetic Variations in Inflammatory Mediators Influence Lung Disease Progression in Cystic Fibrosis
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DOI：
10.1002/ppul.20935
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发表时间：
2008-12-01
影响因子：
3.1
通讯作者：
Clement, Annick
中科院分区：
文献类型：
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作者：
Corvol, Harriet;Boelle, Pierre-Yves;Clement, Annick
囊性纤维化（CF）的临床过程在携带相同CF引起基因突变的患者之间差异很大。由于气道炎症是CF病理生理学的关键组成部分，因此我们研究了主要细胞因子变体是否代表年轻CIF患者中的此类修饰剂。我们检测了在炎症反应中起关键作用的8个基因的13种多态性：肿瘤坏死因子、α-光毒素、白细胞介素（IL）1B、IL 1受体拮抗剂、IL 6、IL 8、IL 10和转化生长因子β 1（TGFB 1），以研究329例CF患者的肺部疾病进展和营养状况。TGFB 1基因+869T/C位点的变异与肺功能下降显著相关。与携带TGFB 1 + 869 TT或+869 CC基因型的患者相比，在TGFB 1 + 869（+869 CT）杂合子患者中观察到1秒用力呼气量（FEV 1）和用力肺活量（FVC）下降率不太明显。这些发现支持TGFB 1基因变异似乎是CF Pediatr Pulmonol中肺部疾病进展的重要遗传修饰因子的概念。2008; 43：1224-1232. (c)2008 Wiley-Liss，Inc.
The clinical course of cystic fibrosis (CF) varies considerably among patients carrying the same CF-causing gene mutation. Additional genetic modifiers may contribute to this variability As airway inflammation is a key component of CF pathophysiology, we investigated whether major cytokine variants represent such modifiers in young CIF patients. We tested 13 polymorphisms in 8 genes that play a key role in the inflammatory response: tumor necrosis factor, lymphotoxin alpha, interleukin (IL) 1B, IL1 receptor antagonist, IL6, IL8, IL10 and transforming growth factor beta 1 (TGFB1), for an association with lung disease progression and nutritional status in 329 CF patients. Variants in the TGFB1 gene at position +869T/C demonstrated a significant association with lung function decline. A less pronounced rate of decline in forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) were observed in patients heterozygous for TGFB1 +869 (+869CT), when compared to patients carrying either TGFB1 +869TT or +869CC genotypes. These findings support the concept that TGFB1 gene variants appear to be important genetic modifiers of lung disease progression in CF Pediatr Pulmonol. 2008; 43:1224-1232. (c) 2008 Wiley-Liss, Inc.