| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
|
|
|
|
|||||||||||||
|
|
|||||||||||||||
Department of
Paediatrics, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK
Correspondence to: Dr J Hull.
Received 2 April 1998; Returned to authors 6 July 1998; Revised version received 21 July 1998; Accepted for publication 17 August 1998
BACKGROUND
Disease severity in patients with
cystic fibrosis shows marked variability. Attempts to explain this
phenotypic heterogeneity on the basis of CFTR genotype have had limited
success. A study was undertaken to test the hypothesis that naturally
occurring variants of the pro-inflammatory cytokine tumour necrosis
factor alpha (TNF-
) and the detoxifying enzyme glutathione
S-transferase M1 (GSTM1) could influence disease severity in cystic fibrosis.
METHODSFifty three children with cystic fibrosis
were studied. To allow for the effect of age, all clinical details were
collected during the eighth year of age. The subjects were divided into groups, both according to the presence or absence of the TNF2 TNF-
-308 promoter polymorphism (n = 20), and by homozygosity for the null
allele of GSTM1 (n = 26).
RESULTSPercentage predicted forced expiratory
volume in one second (FEV1) and weight z
scores were significantly lower in the TNF2 group (mean difference
(95% confidence intervals) for FEV1 11.6% (1.7 to 21.5)
and 0.59 (0.06 to 1.12) for weight z score). The Chrispin-Norman chest radiographic score was significantly higher and
the Shwachman score was significantly lower in patients homozygous for
the GSTM1 null allele.
CONCLUSIONSTwo independent genetic factors have
been identified which appear to influence disease severity in cystic
fibrosis. These results support the contention that inflammation in
cystic fibrosis contributes to tissue damage. Isolation of further such
factors may lead to identification of patients at risk of more severe disease and allow targeted aggressive therapy in this group.
This article has been cited by other articles:
|
|
 |
|
  K. Buranawuti, M. P Boyle, S. Cheng, L. L Steiner, K. McDougal, M D. Fallin, C. Merlo, P. L Zeitlin, B. J Rosenstein, P. J Mogayzel Jr, et al. Variants in mannose-binding lectin and tumour necrosis factor {alpha} affect survival in cystic fibrosis J. Med. Genet., March 1, 2007; 44(3): 209 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Boyle Strategies for Identifying Modifier Genes in Cystic Fibrosis Proceedings of the ATS, January 1, 2007; 4(1): 52 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Laki, I. Laki, K. Nemeth, R. Ujhelyi, O. Bede, E. Endreffy, K. Bolbas, K. Gyurkovits, E. Csiszer, E. Solyom, et al. The 8.1 ancestral MHC haplotype is associated with delayed onset of colonization in cystic fibrosis Int. Immunol., November 1, 2006; 18(11): 1585 - 1590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. F. McKone, J. Shao, D. D. Frangolias, C. L. Keener, C. A. Shephard, F. M. Farin, M. R. Tonelli, P. D. Pare, A. J. Sandford, M. L. Aitken, et al. Variants in the Glutamate-Cysteine-Ligase Gene Are Associated with Cystic Fibrosis Lung Disease Am. J. Respir. Crit. Care Med., August 15, 2006; 174(4): 415 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Drumm, M. W. Konstan, M. D. Schluchter, A. Handler, R. Pace, F. Zou, M. Zariwala, D. Fargo, A. Xu, J. M. Dunn, et al. Genetic Modifiers of Lung Disease in Cystic Fibrosis N. Engl. J. Med., October 6, 2005; 353(14): 1443 - 1453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J de Gracia, F Mata, A Alvarez, T Casals, S Gatner, M Vendrell, D de la Rosa, L Guarner, and E Hermosilla Genotype-phenotype correlation for pulmonary function in cystic fibrosis Thorax, July 1, 2005; 60(7): 558 - 563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Yarden, D Radojkovic, K De Boeck, M Macek Jr, D Zemkova, V Vavrova, R Vlietinck, J-J Cassiman, and H Cuppens Association of tumour necrosis factor alpha variants with the CF pulmonary phenotype Thorax, April 1, 2005; 60(4): 320 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.C. Boucher New concepts of the pathogenesis of cystic fibrosis lung disease Eur. Respir. J., January 1, 2004; 23(1): 146 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.M. Jones, L. Martin, R.J. Bright-Thomas, M.E. Dodd, A McDowell, K.L. Moffitt, J.S. Elborn, and A.K. Webb Inflammatory markers in cystic fibrosis patients with transmissible Pseudomonas aeruginosa Eur. Respir. J., September 1, 2003; 22(3): 503 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Wallace, P. M. Barker, and K. W. Southern Nasal Airway Ion Transport and Lung Function in Young People with Cystic Fibrosis Am. J. Respir. Crit. Care Med., September 1, 2003; 168(5): 594 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Witt Chronic pancreatitis and cystic fibrosis Gut, May 1, 2003; 52(90002): ii31 - 41. [Abstract] [Full Text]
|
|
|
|
|
|
F. J. Accurso and M. K. Sontag Seeking Modifier Genes in Cystic Fibrosis Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 289 - 290. [Full Text] [PDF]
|
|
|
|
|
|
N. Aldallal, E. E. McNaughton, L. J. Manzel, A. M. Richards, J. Zabner, T. W. Ferkol, and D. C. Look Inflammatory Response in Airway Epithelial Cells Isolated from Patients with Cystic Fibrosis Am. J. Respir. Crit. Care Med., November 1, 2002; 166(9): 1248 - 1256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Snyder, M. E. McPherson, J. F. Hunt, M. Johnson, J. S. Stamler, and B. Gaston Acute Effects of Aerosolized S-Nitrosoglutathione in Cystic Fibrosis Am. J. Respir. Crit. Care Med., April 1, 2002; 165(7): 922 - 926. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Gabolde, D Hubert, M Guilloud-Bataille, C Lenaerts, J Feingold, and C Besmond The mannose binding lectin gene influences the severity of chronic liver disease in cystic fibrosis J. Med. Genet., May 1, 2001; 38(5): 310 - 311. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. Kube, U. Sontich, D. Fletcher, and P. B. Davis Proinflammatory cytokine responses to P. aeruginosa infection in human airway epithelial cell lines Am J Physiol Lung Cell Mol Physiol, March 1, 2001; 280(3): L493 - L502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Desmarquest, D. Feldmann, A. Tamalat, M. Boule, B. Fauroux, G. Tournier, and A. Clement Genotype Analysis and Phenotypic Manifestations of Children With Intermediate Sweat Chloride Test Results Chest, December 1, 2000; 118(6): 1591 - 1597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. MAHADEVA and D. A LOMAS Secondary genetic factors in cystic fibrosis lung disease Thorax, June 1, 2000; 55(6): 446 - 446. [Full Text]
|
|
|
|
|
|
E. M. Williams, R. G. Madgwick, A. H. Thomson, and M. J. Morris Expiratory Airflow Patterns in Children and Adults With Cystic Fibrosis Chest, April 1, 2000; 117(4): 1078 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Gabolde, M Guilloud-Bataille, J Feingold, and C Besmond Association of variant alleles of mannose binding lectin with severity of pulmonary disease in cystic fibrosis: cohort study BMJ, October 30, 1999; 319(7218): 1166 - 1167. [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
