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Published on: July 7, 2017
IL1B polymorphisms modulate cystic fibrosis lung disease
Hara Levy1, Amy Murphy, Fei Zou
1Division of Pulmonary Medicine, Children's Hospital, Boston, MA, USA. hlevy@mcw.edu
Interleukin-1 beta (IL1beta) gene variations are linked to differing lung disease severity in cystic fibrosis (CF) patients with the same CFTR mutation. This suggests IL1beta influences CF pulmonary outcomes.
Area of Science:
- Genetics and Molecular Biology
- Pulmonary Medicine
- Immunology
Background:
- Cystic Fibrosis (CF) exhibits variable pulmonary disease severity despite identical CF transmembrane conductance regulator (CFTR) gene mutations.
- Interleukin-1 (IL-1) gene family variations may contribute to this heterogeneity, impacting Pseudomonas aeruginosa infection in chronic infection models.
Purpose of the Study:
- To investigate the association between single nucleotide polymorphisms (SNPs) in the IL-1 gene cluster and pulmonary disease severity in CF patients homozygous for DeltaF508.
- To identify specific IL-1 gene variants that modulate lung disease progression in cystic fibrosis.
Main Methods:
- Genotyped 58 SNPs in the IL-1 gene cluster in 808 CF subjects (DeltaF508 homozygous) from a joint cohort.
- Defined severe and mild lung disease based on forced expired volume (FEV1) quartiles.
- Performed case-control and family-based association analyses using genotypic data and replicated findings in a second CF cohort.
Main Results:
- SNPs rs1143634 and rs1143639 in the IL1B gene consistently associated with lung disease severity categories and longitudinal progression (P < 0.10) in both study cohorts.
- A significant association was observed in females, with a false discovery rate adjusted joint P-value <0.06 for both SNPs in both case-control and family-based analyses.
- Nine SNPs with moderate effect sizes were initially selected for further testing based on initial analyses.
Conclusions:
- Interleukin-1 beta (IL1beta) is identified as a clinically relevant modulator of lung disease severity in cystic fibrosis.
- Genetic variations in IL1B may explain some of the observed heterogeneity in pulmonary disease progression among CF patients.
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