| Title: | "Epidemiology, radiology, and genetics of nicotine dependence in COPD" |
| Author(s): | Kim DK; Hersh CP; Washko GR; Hokanson JE; Lynch DA; Newell JD; Murphy JR; Crapo JD; Silverman EK; Investigators CG; |
| Address: | "Channing Laboratory, Brigham and Women's Hospital, Boston, MA, USA" |
| ISSN/ISBN: | 1465-993X (Electronic) 1465-9921 (Print) 1465-9921 (Linking) |
| Abstract: | "BACKGROUND: Cigarette smoking is the principal environmental risk factor for developing COPD, and nicotine dependence strongly influences smoking behavior. This study was performed to elucidate the relationship between nicotine dependence, genetic susceptibility to nicotine dependence, and volumetric CT findings in smokers. METHODS: Current smokers with COPD (GOLD stage >/= 2) or normal spirometry were analyzed from the COPDGene Study, a prospective observational study. Nicotine dependence was determined by the Fagerstrom test for nicotine dependence (FTND). Volumetric CT acquisitions measuring the percent of emphysema on inspiratory CT (% of lung <-950 HU) and gas trapping on expiratory CT (% of lung <-856 HU) were obtained. Genotypes for two SNPs in the CHRNA3/5 region (rs8034191, rs1051730) previously associated with nicotine dependence and COPD were analyzed for association to COPD and nicotine dependence phenotypes. RESULTS: Among 842 currently smoking subjects (335 COPD cases and 507 controls), 329 subjects (39.1%) showed high nicotine dependence. Subjects with high nicotine dependence had greater cumulative and current amounts of smoking. However, emphysema severity was negatively correlated with the FTND score in controls (rho = -0.19, p < .0001) as well as in COPD cases (rho = -0.18, p = 0.0008). Lower FTND score, male gender, lower body mass index, and lower FEV1 were independent risk factors for emphysema severity in COPD cases. Both CHRNA3/5 SNPs were associated with FTND in current smokers. An association of genetic variants in CHRNA3/5 with severity of emphysema was only found in former smokers, but not in current smokers. CONCLUSIONS: Nicotine dependence was a negative predictor for emphysema on CT in COPD and control smokers. Increased inflammation in more highly addicted current smokers could influence the CT lung density distribution, which may influence genetic association studies of emphysema phenotypes" |
| Keywords: | "Aged Analysis of Variance Case-Control Studies Chi-Square Distribution Female Forced Expiratory Volume Genetic Predisposition to Disease Humans Linear Models Male Middle Aged Nerve Tissue Proteins/*genetics Phenotype *Polymorphism, Single Nucleotide Prosp;" |
| Notes: | "MedlineKim, Deog Kyeom Hersh, Craig P Washko, George R Hokanson, John E Lynch, David A Newell, John D Murphy, James R Crapo, James D Silverman, Edwin K eng U01 HL089897/HL/NHLBI NIH HHS/ K08HL080242/HL/NHLBI NIH HHS/ U01 HL089856/HL/NHLBI NIH HHS/ R01HL094635/HL/NHLBI NIH HHS/ U01HL089897/HL/NHLBI NIH HHS/ UL1 TR000454/TR/NCATS NIH HHS/ G0701127/MRC_/Medical Research Council/United Kingdom U01HL089856/HL/NHLBI NIH HHS/ Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2011/01/15 Respir Res. 2011 Jan 13; 12(1):9. doi: 10.1186/1465-9921-12-9" |
