Research Article: Polymorphisms in HTR2A and DRD4 Predispose to Smoking and Smoking Quantity

Date Published: January 19, 2017

Publisher: Public Library of Science

Author(s): Gloria Pérez-Rubio, Alejandra Ramírez-Venegas, Valeri Noé Díaz, Leonor García Gómez, Karina Elvira Fabián, Salvador García Carmona, Luis A. López-Flores, Enrique Ambrocio-Ortiz, Rocío Contreras Romero, Noé Alcantar-Ayala, Raúl H. Sansores, Ramcés Falfán-Valencia, Huiping Zhang.

http://doi.org/10.1371/journal.pone.0170019

Abstract

Genes encoding the receptors involved in the dopaminergic and serotonergic pathways are potential candidates in the mechanisms of nicotine addiction.

To identify genetic variants in the promoter regions and exons of the DRD4 and HTR2A genes associated with tobacco smoking and the degree of nicotine addiction in Mexican mestizos.

The study included 438 non-smokers (NS) and 1,157 current smokers, ranked based on their consumption of cigarettes per day (cpd): 574 heavy smokers (HS, >20 cpd) and 583 light smokers (LS, 1–10 cpd). Genotyping was performed for 4 and 8 single nucleotide polymorphisms (SNPs) in the DRD4 and HTR2A genes, respectively.

The C allele of rs1800955 in DRD4 was found to be associated with cigarette smoking in the HS vs. NS and LS vs. NS comparisons (p = 2.34E-03 and p = 1.13E-03, respectively); the association was maintained in the homozygous CC genotype (p = 5.00E-04 and p = 2.00E-04, respectively).

Among Mexican mestizos, the C allele of rs1800955 in the DRD4 gene and the A allele of rs6311 in the HTR2A gene are associated with cigarette smoking, whereas the T allele of rs6313 in HTR2A is associated with cigarette smoking and the degree of nicotine addiction.

Partial Text

According to WHO, cigarette addiction is a chronic disease that evolves with relapses, and it is characterized by the inability to abstain from cigarette consumption, behavior deterioration, craving, a decline in the recognition of problems related to cigarette consumption, and dysfunctional emotional responses. The principal component of cigarettes that causes this disease is nicotine, an alkaloid that acts at the central nervous system level, causing changes in the brain of the smoker. One of the principal effects of nicotine is the alteration of certain neurotransmitter levels, including dopamine and serotonin. Therefore, the genes encoding the receptors involved in the dopaminergic and serotonergic pathways are potential candidates in the mechanisms of nicotine addiction [1, 2].

Nicotine addiction is a central nervous system disease that affects pathways such as the dopaminergic and serotonergic pathways in the brain. Several genetic variants have been reported to be associated with nicotine addiction, suggesting the existence of a genetic component; however, few genetic association studies in populations other than the Caucasian population have explored genetic variants in the dopaminergic and serotonergic pathways. In the DRD4 gene, the most studied SNP is rs1800955, which is located in the promoter region (-521 C/T); in our study, in addition to this SNP, two SNPs located in the promoter (rs3758653 and rs936461) and one in an exon (rs1800443) were included.

Among Mexican mestizos, the C allele of rs1800955 in the DRD4 gene and the A allele of rs6311 in the HTR2A gene are associated with cigarette smoking, whereas the T allele of rs6313 in HTR2A is associated with cigarette smoking and the degree of nicotine addiction.

 

Source:

http://doi.org/10.1371/journal.pone.0170019

 

0 0 vote
Article Rating
Subscribe
Notify of
guest
0 Comments
Inline Feedbacks
View all comments