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Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants influence smoking status in a Bangladeshi population.

Research paper by Nusrat Islam NI Chaity, Taposhi Nahid TN Sultana, Md Mehedi MM Hasan, Ishrat Islam II Shrabonee, Noor Ahmed NA Nahid, Md Saiful MS Islam, Mohd Nazmul Hasan MNH Apu

Indexed on: 07 Mar '21Published on: 07 Mar '21Published in: Pharmacological Reports



Abstract

Past studies have established the association of CHRNA5-A3-B4 gene cluster variants with various smoking behaviors in different ethnicities, yet no such study has been reported in Bengali ethnicity to date. A case-control study with 129 smokers and 111 non-smokers was conducted and genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method aimed to manifest the association of three SNPs in this gene cluster with smoking status (SS) in a Bangladeshi population. The non-synonymous CHRNA5 rs1s6969968 and 3'-UTR variant CHRNA3 rs578776 polymorphisms were found to have a strong association with SS. Carriers of polymorphic 'A' allele of rs16969968 showed 1.51-fold more risk of being smokers (adjusted OR = 1.51, 95% CI 0.88-2.57, p = 0.128); whereas, rs578776 polymorphic 'A' allele carriers showed 0.595-fold less risk of being smokers (adjusted OR = 1.51, 95% CI 0.88-2.57, p = 0.006). Comparing smokers and non-smokers, A/A mutant homozygous genotypes of rs578776 and rs16969968 variants pose 0.369-fold (95% CI 0.177-0.77, p = 0.008) and 3.3-fold (95% CI 0.66-16.46, p = 0.14) more risk for positive SS, respectively. No genotypic association for SS was found with intronic variant CHRNB4 rs11072768 (T/G; adjusted OR = 0.827, 95% CI 0.457-1.499, p = 0.532 and G/G; adjusted OR = 0.992, 95% CI 0.455-2.167, p = 0.985). Combination of rs16969968-positive/rs578776-negative polymorphic variants possesses the risk of positive SS in young adults. Furthermore, two new haplotypes (AAT and AAG) were identified in Bangladeshi population and GAG (OR = 0.45, 95% CI 0.25-0.8, p = 0.006) haplotype was found to be a protective factor for SS. Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants rs16969968 and rs578776 are associated with SS in a Bangladeshi population. Large-scale studies are warranted to establish this genotype-phenotype correlation.