Study of polymorphic variants of the serotonin 2A receptor gene (5-HT2A) and its possible effects on smoking habits of a population from northeastern Brazil

Abstract

ABSTRACT. Previous studies have revealed a genetic component, including genetic polymorphisms in the serotonergic pathway, particularly in the serotonin receptor gene (5-HT2A). The aim of this study was to investigate associations of the T102C (rs6313) and A-1438G (rs6311) polymorphisms with tobacco use in a population from northeastern Brazil. We evaluated these polymorphisms in 135 nonsmokers and 135 smokers using polymerase chain reaction-restricted fragment length polymorphism. The distribution of allele and genotype frequencies and associations of polymorphisms with smoking were assessed with the chi-squared (χ 2 ) test, the Fisher exact test, and odds ratio (OR) with a 95% confidence interval (CI). There were no differences in the distribution of genotype and allele frequencies between nonsmokers and smokers for A-1438G (P = 0.80) and T102C (P = 0.35). However, these SNPs 5HT2A A-1438G and T102C in smoking behavior polymorphisms were significantly associated with habit frequency (A/G: P = 0.02, OR = 6.87, 95%CI = 1.23-38.31, P = 0.04; A/G+G/G: P = 0.04, OR = 3.67, 95%CI = 1.06-12.75, P = 0.07), age of onset (C/C: P = 0.02, OR = 3.26, 95%CI = 1.17-9.07, P = 0.03, and nicotine dependence level (A/G: P = 0.02, OR = 3.28, 95%CI = 1.17-9.18, P = 0.04; A/G+G/G: P = 0.04, OR = 2.81, 95%CI = 1.13-6.99, P = 0.04; T/C: P = 0.03, OR = 3.12, 95%CI = 1.13-8.57, P = 0.04; T/C+C/C: P = 0.02, OR = 3.06, 95%CI = 1.22-7.70, P = 0.02). Therefore, these polymorphisms may not contribute significantly to smoking initiation, they do appear to be associated with habit maintenance.

Prevalence of Some Genetic Risk Factors for Nicotine Dependence in Ukraine

“…The rs6313∗C allele carriage is associated with decreased expression of 5-HT2A receptors. In different studies, either C or T alleles were associated with smoking status and intensity [23, 24]. The frequency of rs6313∗TT genotype in Ukraine is 11.3%, the data correspond to the Finnish population, as well as to mixed groups of European, South American, African, and South Asian origins.…”

Association between T102C 5‐HT2A receptor gene polymorphism and 5‐year mortality risk among Brazilian Amazon riparian elderly population

“…Considering specifically the T102C‐SNP, some investigations described the relationship between the CC genotype or C allele and schizophrenia (Ni et al, ; Vaquero‐Lorenzo et al, ), suicidal behavior (González‐Castro et al, ), alcohol dependence, impulsivity of alcohol dependent‐patients (Jakubczyk et al, ; Wrzosek et al, ), and relapse after alcohol dependency treatment (Jakubczyk et al, ). Associations between CC genotype and smoking (Prado‐Lima et al, ) and nicotine dependence level (Ramos‐Neto et al, ) were also reported. The CC genotype was reported to be associated with Alzheimer's disease (Fehér et al, ) and the occurrence of hallucinations, delusions, psychosis, and aberrant motor behavior in Alzheimer's patients (Pritchard et al, ).…”

“…The T102C SNP occurring in this gene can produce three genotypes: TT, CC, and TC. Previous studies have described an association between the CC genotype, that shows 20% less receptor density on cell membranes, and neuropsychiatric disorders such as schizophrenia (Ni, Lu, Wu, Chen, Yi, & Zhang, ; Vaquero‐Lorenzo et al, ), psychotic symptoms in Alzheimer's patients (Fehér et al, ), and alcohol and tobacco addiction (Jakubczyk et al, ; Prado‐Lima et al, ; Ramos‐Neto et al, ; Wrzosek et al, ). Dysfunctions of the 5‐HT2A receptor also include brain diseases such as migraine headaches, anxiety, and mental depression (Fidalgo et al, ).In addition, problems with 5‐HT2A can cause cardiovascular diseases related to platelet aggregation and abnormal vascular smooth muscle cell physiology (Machida, Iizuka, & Hirafuji, ).…”