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Title: Cigarette smoking and rheumatoid arthritis
Author: Hutchinson, David
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2003
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The principle aim of this study was to test the hypothesis that heavy smoking is an aetiological factor in RA and generates a distinct subgroup of the disease definable in terms of clinical phenotype, particularly severity. A second aim was to investigate possible molecule mechanisms linking smoking with RA and what I believe to be candidate mechanisms involving the detoxifying glutathione S transferase Mu 1 (GST M1) gene and oxidative damage to alpha 1 proteinase (alpha1 PI). These studies involved a review of the literatures regarding the link between RA and both smoking and alpha1 PI deficiency. I investigated the relationship between heavy cigarette smoking and hospital based, more severely affected RA patients. Additionally, the age of onset and smoking history was compared in familial and sporadic RA cases. Regarding smoking and severity of RA, a cohort of RA patients were studied to determine if smoking was an independent risk factor for severe RA and whether this effect was influenced by the presence (GSTM1-1) or absence (GSTM1-0) of the GST M1 gene. Oxidative damage in RA to the alpha1 PI protein was studied in relation to rheumatoid disease activity, GST M1 and cigarette smoking. The oxidative damage to alpha1 PI was measured in terms of serum levels of Immunoglobulin A-1 PI was measured in terms of serum levels of Immunoglobulin A-alpha1 PI (IgA-alpha1 PI). In summary, I have shown that heavy smoking is strongly associated with hospital based RA. Secondly, that familial RA presents at an earlier age than sporadic RA in individuals smoking at disease onset only, and that sporadic RA patients are significantly more likely to smoke at disease onset that familial RA patients. I have confirmed previous findings that raised serum IgA-alpha1 PI levels are associated with erosive as opposed to non-erosive RA cases.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available