CHRONIC OBSTRUCTIVE PULMONARY DISEASE RISK AND SMOKING CESSATION CHANGES INDUCED BY CHRNA5-A3 AND CHRNB3-A6 VARIATION IN A CHINESE MALE POPULATION
Zhao L1,, Zou L-Y2,, Cheng B-F3, Yu X-J4, Zou J-H5,*, Han W6,*
*Corresponding Author: Dr. Wei Han, Department of Pulmonary Medicine, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghai Mid Road, Qingdao, People’s Republic of China. Tel: +86-185- 6185-7838. E-mail: sallyhan1@163.com. And: Dr. Jian-Hong Zou, Center of Diseases Control of Qingdao Shi-Bei District, No. 3 Deping Road, Qingdao, People’s Republic of China. Tel: +86-185-6185-7599. E-mail: 277517366@qq.com -Long Zhao, Ling-Yan Zou contributed equally to this study.
page: 51

RESULTS

Demographic Characteristics. As shown in Table 1, the demographics and clinical feature distribution of the subjects show that there are significant differences in age, daily smoking volume and the years of smoking distribution between COPD smoking group, COPD absent smoking group, and smoking without COPD group (p 0.001, p <0.001 and p 0.001). For still smoking patients with COPD and non smoking patients with COPD, we discovered marked differences with respect to age and the years of smoking (both p 0.001). These differences were adjusted in subsequent logistic regression analyses. By comparing the ratios of FEV1 and FEV1/FVC, smoking COPD patients are significantly worse than the control group, and these findings are similar in still smoking patients with COPD and non smoking patients with COPD. In the COPD patients, pulmonary function was classified as mild, moderate, severe, and very severe (30.0, 31.4, 26.6 and 12.0%, respectively). Association Between Gene Polymorphisms and COPD Risk in Smokers. We observed all three SNPs were in Hardy-Weinberg equilibrium in the control group (p 0.05). We genotyped the three SNPs (rs3743073, rs667282 and rs4950) in cases and controls and the results are presented in Table 2. No significant associations were found between rs3743073, rs667282 and rs4950 genotypes and COPD risk after adjusting for age, BMI and smoking status. Association Between Gene Polmorphisms and Smoking Cessation in COPD Patients. Associations between gene polymorphisms and smoking cessation in COPD are shown in Table 3. The genotypes of rs667282 and rs4950 showed significant difference between cases and controls without adjustment for potential confounding factors (age, BMI and smoking pack-years). We adjusted for potential confounding factors by means of logistic regression, and then calculated the odds ratios (ORs). The CT genotype of rs667282 demonstrated association with an increased rate of successful smoking cessation compared with the TT genotype [adjusted OR = 0.54, 95% confidence interval (95% CI) = 0.37-0.7, P = 0.001]. The rs4950 AG genotypes were distinctly associated with increased rates of successful smoking cessation (adjusted OR = 0.55, 95% CI = 0.40-0.76, p 0.001). The effect is significant under the assumption of an over dominant mode of inheritance (adjusted OR = 0.58, 95% CI = 0.43-0.79, p 0.001), while the similar significant differences in rs3743073 was not found (p 0.005). We further observed the suspicious influence factor of CHRNA5-A3 (rs 667282) and CHRNB3-A6 (rs4950) on smoking cessation, stratified by age, cigarettes per day (CPD) and initiation age smoking (Table 4 and Table 5, respectively). As show in Table 4, the success rate of quitting smoking increased for older subjects (>60 years) (OR = 0.66, 95% CI = 0.45-0.99, p = 0.042) and light smokers (CPD ≤20) (OR = 0.58, 95% CI = 0.39-0.86, p = 0.007), accompanied by rs667282 CT genotype. In Table 5, we show that the increased rate of successful smoking cessation with rs4950 AG genotypes was more notable in light smokers (CPD ≤20) (OR = 0.65, 95% CI = 0.45-0.92, p = 0.016). There was no significant difference in the stratification of age and initiation age smoking. Association of CHRNA5-A3 and CHRNB3-A6 Poly- morphisms with the GOLD Stage of COPD Patients. The association of rs667282 and rs4950 polymorphisms with the GOLD stage of COPD patients are exhibited in Table 6. In our study, The CT genotype of rs667282 and the AG genotype of rs4950 showed a weak association with the GOLD stage of COPD patients.



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