Balkan Journal of Medical Genetics

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

INTRODUCTION

Investigating chronic obstructive pulmonary disease (COPD) and smoking cessation is a continuing concern within pulmonology. Its mortality i expected to be ranked fourth in the world by 2030 [1]. It is generally believed that smoking is the main risk factor for COPD development, however, only a fraction (~20.0%) of smokers develop COPD [2]. This suggests that individual susceptibility is caused by genetic factors. Previous genetic studies have shown that nicotine-dependence is a complex genetic disorder [3]. We believe that genes related to nicotinedependence may affect the development of COPD. In addition, nicotine-dependence can be considered as the most significant factor for smoking cessation [4]. Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine [5]. Nicotine, a major component of tobacco, is the main cause of tobacco addiction that acts through nAChRs. At present, genome-wide association studies have proved that several single nucleotide polymorphisms (SNPs) (rs1051730, rs16969968, rs8034191 and rs4950) in two nAChRs (CHRNA5-A3 and CHRNB3-A6) subunit coding gene clusters are associated with nicotine-dependence and lung cancer [6-10]. In addition, according to the HapMap database (https://www.ncbi.nlm.nih.gov/probe/ docs/ projhapmap/) and a study by Wu et al. [11], there is no report that these three SNP variants have been found in Asian populations. These variants have little risk of lung cancer and nicotine-dependence in the Chinese population. Surprisingly, the results of two independent studies show that rs667282 and rs3743073 in CHRNA5-A3 will affect the risk of lung cancer in Chinese people [11,12]. Moreover, several independent studies have shown that rs4950 in CHRNB3-A6 is with smoking behavior, and this shows that they have a certain role in people who have difficulty in quitting smoking and people who are carcinogenic due to smoking [9,10]. Thus far, no research has reported if the three SNPs are also associated with smoking-related COPD and smoking cessation. Therefore, this study aimed to investigate the correlation between the three SNPs (rs667282, rs3743073 and rs4950) and smoking cessation in the Chinese male population.

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