CHRNA4 rs1044396 is associated with smoking cessation in varenicline therapy

Abstract

Background: The large individual variability in response to drugs for smoking cessation suggests that specific treatments can be more effective in particular subgroups of smokers. In the context of personalized medicine, the main aim of the present study was to evaluate whether the CHRNA4 and CHRNB2 polymorphisms are associated with response to smoking cessation therapies in patients from a smoker assistance program.Methods: This cohort study enrolled 483 smoking patients who received behavioral counseling and drug treatment (varenicline, bupropion, and/or nicotine replacement therapy). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. Fagerström test for nicotine dependence (FTND) and Issa situational smoking scores were analyzed for nicotine dependence. The CHRNA4 (rs1044396 and rs2236196) and CHRNB2 (rs2072660 and rs2072661) polymorphisms were genotyped by high resolution melting analysis.Results: Patients with rs1044396 CC genotype had lower success rate in treatment with varenicline (29.5%) compared with carriers of CT or TT genotypes (50.9%; p = 0.007, n = 167). The CT or TT genotypes were associated with higher odds ratio for success (OR = 1.67, 95% CI = 1.10–2.53, p = 0.02), in a multivariate model. We did not observe significant differences in the FTND and Issa scores according to the studied polymorphisms.Conclusion: The CHRNA4 rs1044396 is associated with smoking cessation in individuals on varenicline therapy. We suggest that this polymorphism influences the varenicline response, but replications of this finding are needed.

Cholinergic receptor nicotinic alpha 5 subunit polymorphisms are associated with smoking cessation success in women

“…Many studies have identified the association of polymorphisms in the CHRNA5-A3-B4 gene with smoking cessation in response to smoking cessation therapies [ 2 , 29 – 31 ]. Recently, our group of researchers found the association of the CHRNA4 rs10443196 and cytochrome P450 2B6 ( CYP2B6) 785A > G polymorphisms with a higher success rate in varenicline and bupropion treatment, respectively [ 32 , 33 ].…”

The association between the nicotinic acetylcholine receptor α4 subunit gene (CHRNA4) rs1044396 and Internet gaming disorder in Korean male adults

“…The present study identified the influence of the gene coding for the alpha4 subunit of the nicotinic acetylcholine receptor ( CHRNA4 ) on IGD. With respect to addiction, a biological link between CHRNA4 and the nicotine-addiction phenotype has been established [ 21 , 49 – 51 ]. Knock-in mice with a point mutation in the CHRNA4 gene showed reduced nigrostriatal dopaminergic function [ 52 ].…”

“…To address this assumption, the present study conducted two case-control studies of IGD and AD using the same candidate genes, but the results do not support the assumption. Although rs1044396 of the CHRNA4 gene was associated with nicotine addiction and the addiction phenotype [ 21 , 49 – 51 , 55 ], further association, family-aggregation, or twin studies are needed to examine the extent to which IGD shares a common genetic vulnerability with substance addictions.…”

Relative contribution of genetic, individual, and self-efficacy factors to smoking cessation in a Chinese rural population

“…Tobacco dependence does not just mean physical dependence, it also means psychological dependence . Previous studies revealed genetic, individual, and psychological factors significantly contribute to smoking behavior . A solid body of evidence showed that nicotine, the major addictive component of tobacco, induces continuous tobacco use and dependence .…”

“…Nicotine initiates its effects by binding to nicotinic acetylcholine receptors (nAChRs) that were coded by nicotinic acetylcholine receptor genes (CHRN). Single nucleotide polymorphisms (SNPs) in CHRNA3‐CHRNA5‐CHRNB4, CHRNA4‐CHRNB2, and CHRNA6‐CHRNB3 have been found to be related to SC. However, these articles only investigated the relationships between single SNP in CHRN genes and SC, which results in two possible limitations.…”