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

doi:10.1186/1465-9921-8-88

Respiratory Research

Volume 8

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Corvol H
Nathan N
Charlier C
Chadelat K
Le Rouzic P
Tabary O
Fauroux B
Henrion-Caude A
Feingold J
Boelle PY
Clement A

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Corvol H
Nathan N
Charlier C
Chadelat K
Le Rouzic P
Tabary O
Fauroux B
Henrion-Caude A
Feingold J
Boelle PY
Clement A
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Research

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

Harriet Corvol¹^,2^,3 , Nadia Nathan¹^,2^,3 , Celine Charlier¹^,2^,3 , Katarina Chadelat¹^,2^,3 , Philippe Le Rouzic¹^,2^,3 , Olivier Tabary¹^,2^,3 , Brigitte Fauroux¹^,2^,3 , Alexandra Henrion-Caude¹^,2^,3 , Josue Feingold¹^,4 , Pierre-Yves Boelle¹^,2^,5 and Annick Clement¹^,2^,3

¹Université Pierre et Marie Curie-Paris6, Paris, 75571 France

²Inserm, UMR-S 707, Paris, 75000 France

³AP-HP, Hôpital Trousseau, Pediatric Pulmonary Department, Paris, 75571 France

⁴AP-HP, Hôpital Trousseau, Genetics Department, Paris, 75571 France

⁵AP-HP, Hôpital St. Antoine, Biostatistics Department, Paris, 75571 France

author email corresponding author email

Respiratory Research 2007, 8:88doi:10.1186/1465-9921-8-88


Published:	29 November 2007

Abstract

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 FEV₁and 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).

Conclusion

The BclI polymorphism may modulate the inflammatory burden in the CF lung and in this way influence progression of lung function.