Association of polymorphisms of the genes HTR2A and 5-HTT with smoking in Yakuts

Tobacco smoking is the most common form of addiction worldwide. The aim of our study was to determine whether the rs6311 polymorphisms of the HTR2A gene and the 5HTTLPR and rs25531 polymorphisms of the 5-HTT gene are associated with smoking in the Yakut population. The study involved 223 people, including 115 smokers and 108 non-smokers. The results of the analysis of the relationship between the rs6311 polymorphism of the HTR2A gene and smoking showed that in the group of smokers, allele A was somewhat more common than in the group of non-smokers (OR - 1.138, 95% CI = [0.742-1.138]). Analysis of the distribution of alleles and genotypes of the 5-HTTLPR polymorphism of the 5-HTT gene showed the predominance of the short S allele (74.8–89.4%) and the SS genotype (61.7–81.5%) in both samples. Smokers had a significantly (p<0.05) higher frequency of the risk allele L (OR -2.830, 95% CI= [1.674 -4.783]) compared to non-smokers. When analyzing the 5-HTTLPR and rs25531 polymorphisms grouped into groups, it was found that the frequency of the L' allele was four times higher in the sample of smokers (p<0.001) than in the sample of non-smokers (OR -4.844, 95% CI = [2.503-9.372]). An analysis of the distribution of combinations of genotypes of both studied genes showed the predominance of people with a combination of GG genotypes of the HTR2A gene and S'S' of the 5-HTT gene, which showed a protective effect on smoking (OR -0.550, 95% CI = [0.319-0.948]). A significant association with smoking was shown by a combination of heterozygous genotypes AG of the HTR2A gene and L'S' of the 5-HTT gene (OR -13.637, 95% CI= [1.752-106.144]). This study established a significant association of 5-HTT gene polymorphisms with smoking in the Yakut population. In connection with the equivalent serotonin expression of the S and LG alleles, 5HTTLPR and rs25531 polymorphisms, it is more informative to carry out their generalized analysis.

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