Glucocorticoid receptor gene polymorphisms associated with progression of lung disease in young patients with cystic fibrosis.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
The BclI polymorphism may modulate the inflammatory burden in the CF lung and in this way influence progression of lung function.
Université Pierre et Marie Curie-Paris6, Paris, 75571 France. harriet.corvol@trs.aphp.fr
Harriet
H
Corvol
Nadia
N
Nathan
Celine
C
Charlier
Katarina
K
Chadelat
Philippe
P
Le Rouzic
Olivier
O
Tabary
Brigitte
B
Fauroux
Alexandra
A
Henrion-Caude
Josue
J
Feingold
Pierre-Yves
PY
Boelle
Annick
A
Clement
D000293:Adolescent; D002648:Child; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology*; D015252:Deoxyribonucleases, Type II Site-Specific; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008171:Lung Diseases / Q000382:microbiology / Q000503:physiopathology*; D008297:Male; D011110:Polymorphism, Genetic; D011552:Pseudomonas Infections; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012129:Respiratory Function Tests
D011965:Receptors, Glucocorticoid; C041666:endodeoxyribonuclease BclI; D015252:Deoxyribonucleases, Type II Site-Specific