Corvol Harriet, Nathan Nadia, Charlier Celine, Chadelat Katarina, Le Rouzic Philippe, Tabary Olivier, Fauroux Brigitte, Henrion-Caude Alexandra, Feingold Josue, Boelle Pierre-Yves, Clement Annick
Université Pierre et Marie Curie-Paris6, Paris, 75571 France.
Respir Res. 2007 Nov 29;8(1):88. doi: 10.1186/1465-9921-8-88.
The variability in the inflammatory burden of the lung in cystic fibrosis (CF) patients together with the variable effect of glucocorticoid treatment led us to hypothesize that glucocorticoid receptor (GR) gene polymorphisms may affect glucocorticoid sensitivity in CF and, consequently, may contribute to variations in the inflammatory response.
We evaluated the association between four GR gene polymorphisms, TthIII, ER22/23EK, N363S and BclI, and disease progression in a cohort of 255 young patients with CF. Genotypes were tested for association with changes in lung function tests, infection with Pseudomonas aeruginosa and nutritional status by multivariable analysis.
A significant non-corrected for multiple tests association was found between BclI genotypes and decline in lung function measured as the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). Deterioration in FEV1 and FVC was more pronounced in patients with the BclI GG genotype compared to the group of patients with BclI CG and CC genotypes (p = 0.02 and p = 0.04 respectively for the entire cohort and p = 0.01 and p = 0.02 respectively for F508del homozygous patients).
The BclI polymorphism may modulate the inflammatory burden in the CF lung and in this way influence progression of lung function.
囊性纤维化（CF）患者肺部炎症负担存在变异性，且糖皮质激素治疗效果各异，这使我们推测糖皮质激素受体（GR）基因多态性可能影响CF患者对糖皮质激素的敏感性，进而可能导致炎症反应的差异。
我们评估了255例年轻CF患者队列中四种GR基因多态性（TthIII、ER22/23EK、N363S和BclI）与疾病进展之间的关联。通过多变量分析检测基因型与肺功能测试变化、铜绿假单胞菌感染及营养状况之间的关联。
在多次检验未校正的情况下，发现BclI基因型与以一秒用力呼气量（FEV1）和用力肺活量（FVC）衡量的肺功能下降之间存在显著关联。与BclI CG和CC基因型患者组相比，BclI GG基因型患者的FEV1和FVC恶化更为明显（整个队列中p分别为0.02和0.04，F508del纯合患者中p分别为0.01和0.02）。
BclI多态性可能调节CF肺部的炎症负担，从而影响肺功能进展。
