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Exposure to Swine Farming and the Lungs: Gene-Environment Interactions Open Access


Other title
Swine barns
Toll-like receptor 4 (TLR4) gene
Nitric Oxide Synthase 3 (NOS3) gene
Toll-like receptor 2 (TLR2) gene
Gene and environment interaction
Type of item
Degree grantor
University of Alberta
Author or creator
Supervisor and department
Ambikaipakan Senthilselvan (Public Health Sciences)
Examining committee member and department
Jeremy Beach (Medicine)
Heather E McDermid (Biological Sciences)
Paul Veugelers (Public Health Sciences)
Susanna Von Essen (Internal Medicine, University of Nebraska Medical Center)
Donna C Rennie (Canadian Centre for Health and Safety in Agriculture, University of Saskatchewan)
School of Public Health Sciences
Date accepted
Graduation date
Doctor of Philosophy
Degree level
Occupational exposures in swine operations are associated with increased risk of respiratory problems. Although the etiology is not fully understood, genetic and environmental factors play important roles. The primary objective of this thesis is to explore effects of polymorphisms in the Toll-like receptor 2 (TLR2), TLR4 and Nitric Oxide Synthase 3 (NOS3) genes on lung function among workers in swine operations (a high exposure group) and non-farming rural residents (a low exposure group). The studies considered in this thesis were a cross-sectional study of 374 full-time workers and 411 non-farming rural dwellers in 2003/04, and a longitudinal study of 302 workers and 261 non-farming rural dwellers who were initially studied in 1990/91 and were followed up in 1994/95 (217 workers and 171 rural dwellers) and in 2003/04 (173 workers and 119 rural dwellers). Information on demographic and lifestyle factors and lung function measurements were collected at the three time points and blood samples for genotyping were obtained in 2003/04. The important findings in this study were: (1) Workers with TLR2-16933T/A polymorphism (AA) had greater mean values of lung function than workers with the wild-type (AT+TT) (FEV1 (L): 3.7 vs. 3.5, p=0.009; FEF25%-75% (L/s): 3.7 vs. 3.3, p=0.003); similar associations were also observed for the TLR2Arg677Trp polymorphism among workers; (2) Workers with NOS3-786T/C polymorphism (CC) had greater mean values of lung function than workers with the wild-type (TC+TT) (FEV1 (L): 3.75 vs. 3.55, p=0.009; FVC (L): 4.79 vs. 4.56, p=0.03); similar associations were also observed for the NOS3Glu298Asp polymorphism among workers; (3) Workers with NOS3-786T/C polymorphism (CC) had a lower annual decline rates in FEV1 (-30.5 ml/year vs. -58.0 ml/year, p=0.005) and FVC (-16.7 ml/year vs. -50.9 ml/year, p=0.01) than workers with TT genotype; and (4) None of these associations were observed in non-farming rural dwellers. In conclusion, TLR2 and NOS3 polymorphisms had significantly protective effects on lung function among workers in swine operations. The results from this study will increase our understanding of environmental and genetic determinants of respiratory dysfunction and ultimately lead to better prevention and intervention measures to improve the respiratory health of workers in swine operations.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Gao Z, Rennie D, Senthilselvan A (2010). Allergic rhinitis and genetic components: Focus on toll-like receptors (TLRs) gene polymorphism. The Application of Clinical Genetics. 2010. Nov; 2010(3):109-120.Gao Z, Dosman JA, Rennie DC, Schwartz DA, Yang IV, Beach J, Senthilselvan A. Association of Toll-like receptor 2 gene polymorphisms with lung function in workers in swine operations. Ann Allergy Asthma Immunol. 2013 Jan:110(1):44-50.

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