Abstract
Tobacco smoking is a major risk factor of several diseases such as lung cancer, stroke, chronic obstructive pulmonary disease and increases the susceptibility to infectious diseases. The understanding of smoking addiction requires phenotyping and genotyping studies. Variations in CHRNA5/CHRNA3 can alter receptor responses to nicotine and thus interfere with smoking behavior and risk. Therefore, this study aimed to investigate the association of CHRNA5 rs16969968 and CHRNA3 rs578776 with smoking behavior in a Brazilian population sample, comprising 449 subjects. Smoking data was obtained from a questionnaire. The polymorphisms were genotyped by Polymerase Chain Reaction (PCR). Associations were verified using logistic and linear regression analyses. We found that women with the variant AA genotype for CHRNA5 rs16969968 were at significantly increased risk of smoking, with an OR of 3.09 (95% CI: 1.09-8.76; p= 0.033). The variant TT genotype of CHRNA3 rs578776 showed protection against smoking and later smoking initiation in the overall population and in women, with an OR of 0.41 (95% CI: 0.19-0.88; p=0.022). In conclusion, CHRNA5 rs16969968 and CHRNA3 rs578776 were associated with increased risk and protective effect against smoking, respectively, in a Brazilian population sample. Gender and recessive homozygosis of the polymorphisms variants resulted in a significant effect regarding the results.
Highlights
Smoking is a worldwide problem Public Health responsible for over 8 million deaths a year
Possible associations between CHRNA5 rs16969968 and CHRNA3 rs578776 single nucleotide polymorphisms (SNPs) and the risk of smoking and smoking behavior in a Brazilian population were evaluated, since these SNPs have been linked to interindividual variability concerning nicotine responses
Few studies focusing on the interference of genetic variations in smoking initiation of smoking are available, the findings reported were in accordance with other assessments [12,13,14,37,38], who reported that people who began smoking earlier exhibited a greater risk of smoking dependence
Summary
Smoking is a worldwide problem Public Health responsible for over 8 million deaths a year. Cigarettes are the main source of tobacco consumption, containing over 7000 different chemical substances [2]. Nicotine is the major tobacco substance that establishes and maintains cigarette smoking dependence [3]. Nicotine is an acetylcholine agonist that binds to nicotinic acetylcholine receptors (nAChRs). These receptors are formed by subunits and are distributed in the central and peripheral nervous system, as well as other tissues such as muscle and the endothelium. The arrangement between subunits results in receptors differentially distributed throughout the Corresponding author: Mota Caroline de Lima Department of Toxicogenetics, Center for Studies of Worker’s Health and Human Ecology, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
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