Genetic variation as a predictor of smoking cessation success. A promising preventive and intervention tool for chronic respiratory diseases?

Abstract

Tobacco smoking continues to be the largest preventable cause of premature morbidity and mortality throughout the world, including chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease. Although most smokers are highly motivated to quit and many smoking cessation therapies are available, cessation rates remain very low.Recent research strongly suggests that variation in genetic background is an important determinant of smoking behaviour and addiction. Since these genetic variants might also influence the response to smoking cessation pharmacotherapies, it is likely that assessment of genetic background could be a promising tool to guide selection of the most effective cessation treatment for an individual smoker. Recently, it has been shown that genetic variants in the dopaminergic system, opioid receptors, the bupropion-metabolising enzyme CYP2B6 and the nicotine-metabolising enzyme CYP2A6 may play an important role in predicting smoking cessation responses to nicotine replacement therapy and bupropion treatment. Despite the progress that has been made, several challenges will still have to be overcome before genetically tailored smoking cessation therapy can be implemented in standard clinical practice.

Genetics of smoking and depression

“…Interestingly, one of the most commonly studied polymorphisms is the 5-HTTLPR region of the SLC6A4 gene. In addition to possible relationships between depression and this region, there is evidence that nicotine receptor activation can increase serotonin release (Li et al 1998), and a link between 5-HTTLPR genotype expression and smoking has been observed (Quaak et al 2009). In a study of 185 current smokers, Lerman et al (2000) observed a positive association between neuroticism and smoking behaviors in individuals with S expression of the 5-HTTLPR region, but not those with the L genotype.…”

Association of serotonin transporter gene variation with smoking, chronic obstructive pulmonary disease, and its depressive symptoms

“…However, this is the first report on an association between SLC6A4 SNPs and COPD. SLC6A4 is thought to be closely related to nicotine dependence 4 and has been reported to be associated with smoking behaviour in the Japanese 8 and Chinese. 9 CYP2A6 and CHRNA 3/5 are believed to be candidate genes involved in COPD pathogenesis, 5,6 there are no reports on an association between SLC6A4 and COPD.…”

“…7 SLC6A4 is thought to be closely related to nicotine dependence 4 and smoking behaviour in the Japanese 8 and Chinese. 9 SLC6A4 variation has also been reported to be related to depression.…”

“…3 Some genes related to nicotine dependence, including nicotine receptors and those involved in the dopamine and serotonin pathways, 4 are believed to be good candidates for genetic risk factors of COPD. CYP2A6 and a-nicotinic acetylcholine receptor (CHRNA 3/5) were investigated as candidate genes involved in COPD pathogenesis; 5,6 however, the association between many genes and COPD remains to be studied.…”

Comment on: Effect of a nicotine-free inhalator as part of a smoking cessation programme

“…Better diagnosis of the smokers, which this study aims for, could ultimately lead to tailoring treatments and boosting efficacy [3]. This first study was small and needs to be replicated with larger samples and by other investigators.…”