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Title: Genetic polymorphism in proinflammatory cytokines in bronchiectasis
Author: Anwar, Ghazanfar Ali
ISNI:       0000 0004 2738 8543
Awarding Body: University of Newcastle Upon Tyne
Current Institution: University of Newcastle upon Tyne
Date of Award: 2011
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Bronchiectasis is a disease characterised by chronic bronchial sepsis and exerts considerable morbidity in those affected. In approximately 50% of cases the aetiology is unknown (idiopathic), raising the possibility of genetic predisposition. Cytokines such as IL-1, IL-6, IL-8 and TNFα are potent neutrophil recruiting molecules and are abundant in bronchiectatic secretions. Cytokine polymorph isms can lead to constitutively high production, and have been associated with a number of chronic inflammatory states. Hypothesis: Gene polymorph isms associated with high cytokine production predispose to idiopathic bronchiectasis (IB). Aims and objectives: To determine if high production alleles of cytokines IL-1β, IL6, IL8, TNF and IFNG are associated with idiopathic bronchiectasis (I B). Frequencies of these alleles were compared in patients with IB, bronchiectasis of known cause and normal controls. Allele frequencies in IB were also correlated with clinical markers of disease severity. Methods Following ethical approval, prospectively recruited patients underwent extensive clinical. phenotyping. IB was established as a diagnosis of exclusion. Allele frequencies for candidate genes were determined by PCR, with control allele frequencies available from local blood donors. Comparisons were made by Chi Square tests. Results: 189 patients (95f, 94m), mean (SO) age 66.11 (11.52) years were recruited including 82 (43%) idiopathies, No differences in the candidate allele frequencies were found between IB with 200+ controls and bronchiectasis of known cause group (n=1 06). Within idiopathic group, IL8+781T, IL6-174C, and IL1B-511T alleles were significantly associated with daily sputum production. In addition, IL8+781T and IL6-174C were associated with high exacerbation frequency and positive Pseudomonas aeruginosa culture. IL-1 B+3953T was significantly under- represented in those with daily sputum production and positive Pseudomonas status. Conclusions: Gene polymorphisms predisposing to high cytokine production were not found to be associated with lB. Several alleles were found to significantly associated with more severe disease. Independent confirmation is required in an adequately powered study.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available