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 Sandford1
1University 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 work
Background: 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 results suggest interactions of IL6 rs2069825 and IFNG rs2069727 single nucleotide polymorphisms with cigarette smoking on measures of lung function. The IL6 rs2069825 single nucleotide polymorphism also interacted with smoking to affect the risk of cardiovascular disease in COPD patients.
Keywords: gene-environment interactions, interleukin-6, forced expiratory volume in one second, cardiovascular disease, chronic obstructive pulmonary disease