Association of genetic variations in the CSF2 and CSF3 genes with lung function in smoking-induced COPD

¹ The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St. Paul's Hospital, University of British Columbia, Vancouver, B.C., Canada
² Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
³ Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

^* To whom correspondence should be addressed. E-mail: asandford{at}mrl.ubc.ca.

	Abstract

Granulocyte-macrophage colony-stimulating factor (CSF2) and G-CSF (CSF3) are important survival and proliferation factors for neutrophils and macrophages. The objective of this study was to determine whether single nucleotide polymorphisms (SNPs) of CSF2 and CSF3 are associated with lung function in smoking induced COPD.

Five SNPs of CSF2 and CSF3 were studied in 587 non-Hispanic whites with the fastest (n=281) or the slowest (n=306) decline of lung function selected from among continuous smokers in the NHLBI Lung Health Study (LHS). These SNPs were also studied in 1074 non-Hispanic whites with the lowest (n=536) or the highest (n=538) baseline lung function at the beginning of the LHS.

An increase in the number of CSF3 -1719T alleles was associated with protection against low lung function, odds ratio (OR)=0.73, 95% confidence interval (CI)=0.56 to 0.95, P=0.018 and was still significant after adjustment for multiple comparisons. There was also a significant association of a CSF3 haplotype with baseline FEV₁ levels (global test p=0.004 and 0.027 before and after adjustment for confounding factors). No association was found for CSF2 SNPs and lung function, nor was there evidence of epistasis.

Genetic variation in CSF3 is associated with cross-sectionally measured lung function in smokers.