Effect of gene environment interactions on lung function and cardiovascular disease in COPD

Tillie-Louise Hackett1,2,*, Dorota Stefanowicz1,*, Farzian Aminuddin1, Don D Sin1, John E Connett3, Nicholas R Anthonisen4, Peter D Paré1, Andrew J Sandford11University of British Columbia, James Hogg Research Laboratories, St Paul's Hospital, Division of Respirology, Department of Medicine, 2Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, BC, Canada; 3School of Public Health, University of Minnesota, Minneapolis, MN, USA; 4Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada*These authors contributed equally to this workBackground: The objective of this study was to determine if gene-environment interactions between cigarette smoking and interleukin-6 (IL6), interferon-γ (IFNG), interleukin-1β (IL1B), or interleukin-1 receptor antagonist (IL1RN) single nucleotide polymorphisms are associated with lung function decline and cardiovascular disease in chronic obstructive pulmonary disease (COPD).Methods: Single nucleotide polymorphisms (SNPs) in IL6, IFNG, IL1B, and IL1RN were genotyped in the Lung Health Study and correlated with rate of decline of forced expiratory volume in 1 second (FEV1) over 5 years, baseline FEV1, serum protein levels, cardiovascular disease, and interactions with smoking.Results: The IL6 rs2069825 single nucleotide polymorphism was associated with the rate of decline of prebronchodilator FEV1 (P = 0.049), and was found to have a significant interaction (P = 0.004) with mean number of cigarettes smoked per day. There was also a significant interaction of IFNG rs2069727 with smoking on prebronchodilator (P = 0.008) and postbronchodilator (P = 0.01) FEV1. The IL6 polymorphism was also associated with cardiovascular disease in heterozygous individuals (P = 0.044), and was found to have a significant interaction with smoking (P = 0.024). None of the genetic variants were associated with their respective serum protein levels.Conclusion: The res