Influence of C-159T SNP of the CD14 gene promoter on lung function in smokers

Zhou, Haibo; Alexis, Neil E.; Almond, Martha; Donohue, James; LaForce, Craig; Bromberg, Philip A.; Peden, David B.

doi:10.1016/j.rmed.2009.03.007

« Previous Next »Respiratory Medicine
Volume 103, Issue 9 , Pages 1358-1365, September 2009

Influence of C-159T SNP of the CD14 gene promoter on lung function in smokers

Haibo Zhou
- The Center for Environmental Medicine, Asthma and Lung Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Department of Biostatistics, The Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Corresponding author at: Department of Biostatistics, CB# 7420 McGavran-Greenbery Hall, The Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7420, USA. Tel.: +1 919 966 3885; fax: +1 919 966 3804.
Neil E. Alexis
- The Center for Environmental Medicine, Asthma and Lung Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Department of Pediatrics, The School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Martha Almond
- The Center for Environmental Medicine, Asthma and Lung Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
James Donohue
- Department of Medicine, The School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Craig LaForce
- Department of Pediatrics, The School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- North Carolina Clinical Research, Raleigh, NC, USA
Philip A. Bromberg
- The Center for Environmental Medicine, Asthma and Lung Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Department of Medicine, The School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
David B. Peden
- The Center for Environmental Medicine, Asthma and Lung Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Department of Pediatrics, The School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Department of Medicine, The School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Received 22 September 2008; accepted 12 March 2009. published online 13 April 2009.

Summary

CD14, a co-receptor for endotoxin, plays a significant role in regulating the inflammatory response to this agent. The C-159T single nucleotide polymorphism (SNP) in the CD14 gene promoter is an important regulator of CD14 expression, with TT homozygotes having increased expression of CD14. This SNP has been linked to pathogenesis of asthma and with cardiovascular diseases in smokers. We hypothesize that CD14 also plays a role in the pathophysiology of COPD in smokers who are exposed to endotoxin contained in cigarette smoke as well as endotoxin derived from Gram-negative microbes colonizing their airways. To assess the effect of the C-159T SNP of the CD14 gene promoter on lung function, we recruited 246 smokers 40 years of age or older with a range of 10–156 pack-year smoking exposures. The TT genotype was associated with lower lung function in smokers with a moderate smoking history. However, the CC genotype was associated with decreased lung function in heavy smokers (>56 pack years). The effect of CC genotype on severity of COPD is analogous with the effect of this genotype in risk for asthma. CD14 may be a factor in the pathophysiology of COPD, as it is in asthma and smoking-related cardiovascular diseases.

Keywords: COPD, Gene-environment interaction, Endotoxin, Smoking, CD14