Abstract
BACKGROUND: A recent study has identified the role of CHRNA5-A3-B4 gene cluster variants rs16969968 and rs578776 of nicotinic acetylcholine receptors (nAChRs) on smoking status in Bengali ethnicity. The aim of the current study was to investigate whether these rs16969968-rs578776-rs11072768 single nucleotide polymorphisms (SNPs) of CHRNA5-A3-B4 gene cluster were associated with nicotine dependence (ND) and related phenotypes. METHODS: The Fagerstrom Test for Nicotine Dependence (FTND) and Cigarette Dependence Scale (CDS-12) were used to assess the degree of ND, and genotyping was done using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method on a cohort of 129 male smokers participating in a structured questionnaire-based survey. RESULTS: Smokers with AA genotype of CHRNA5 rs16969968 SNP were at significantly increased risk of developing ND compared to its wild type variant with odds ratio (ORs) of 1.20 (FTND: 95% CI 0.25-5.37, p = 0.253) and 2.48 (CDS-12: 95% CI 0.46-13.26, p = 0.081), respectively. Conversely, smokers with AA genotype of CHRNA3 rs578776 variant had a strong protective effect against ND development (ORs = 0.27, 95% CI 0.09-0.80, p = 0.076). There was no such link reported in CHRNB4 rs11072768 variant carriers. Similarly, G-A/G-A diplotype of rs16969968_rs578776 variants was discovered to be a protective factor against ND. Moreover, demographic features such as age, occupation and dwelling status were found to be significantly associated with ND. CONCLUSION: Taken together, CHRNA5-A3-B4 gene cluster variants rs16969968 and rs578776 as well as specific demographic characteristics regulate ND and related smoking phenotypes in Bangladeshi male smokers. Further studies with large sample sizes are required to substantially validate the significance.