Association of Polymorphism CHRNA5 and CHRNA3 Gene in People Addicted to Nicotine

Abstract

Smoking is a chronic and relapsing addictive trait that harms public health. Among the many identified genetic variants of nicotine dependence, the variants in the CHRNA5/A3/B4 gene cluster on chromosome 15 that encode the α5, α3, and β4 subunits have recently received a lot of attention. Importantly, variants in this gene cluster have been associated with nicotine addiction. Among the many significant variants in this cluster, the polymorphism SNP rs16969968 seems to be the most interesting factor in nicotine addiction. This polymorphism causes an amino acid change from aspartate to asparagine at position 398 of the α5 nicotinic receptor protein sequence. Our study aimed to analyze three polymorphic variants: the rs16969968 located in the CHRNA5 gene, the rs578776 and rs1051730 located in the CHRNA3 gene in nicotine-addicted subjects, and in controls. Our study encompasses an association analysis of genotypes and haplotypes. A group of 401 volunteers was recruited for the study and divided into two groups: the study group consisted of addicted smokers and a control group of 200 unrelated non-smokers who were not dependent on any substance and healthy. A statistically significant difference was observed in the frequency of genotypes of the rs1051730 polymorphism of the CHRNA3 gene (χ2 = 6.704 p = 0.035). The T/T genotype was statistically significantly more frequent in the group of nicotine-dependent subjects. The haplotypes rs16969968, rs578776, and rs1051730 were distinguished, of which the G-T-T and G-C-T haplotypes were present only in the study group. With differences in frequencies, statistical significance was noted—for the G-T-T haplotype p = 0.01284 and the G-C-T haplotype p = 0.00775. The research stated that novel haplotypes G-T-T and G-C-T, though with very low-frequency variants in CHRNA3, were associated with nicotine addiction.