Back to Search
Start Over
CHRNA4 and ANKK1 Polymorphisms Influence Smoking-Induced Nicotinic Acetylcholine Receptor Upregulation
- Publication Year :
- 2016
- Publisher :
- Oxford University Press, 2016.
-
Abstract
- INTRODUCTION Tobacco smoking leads to increased numbers of β2*-containing nicotinic acetylcholine receptors (β2*-nAChRs) throughout the brain, which return to nonsmoker levels over extended abstinence. The goal of the current study was to determine whether the degree of tobacco smoking-induced changes in β2*-nAChR availability is genetically influenced. METHODS In this study, 113 European Americans participated in one or two [(123)I]5-IA-85380 single photon emission computed tomography (SPECT) brain scans. Smokers (n = 58) participated in one scan at 7-9 days of abstinence and those who remained abstinent (n = 27) were imaged again at 6-8 weeks of abstinence. Age- and sex-matched nonsmokers (n = 55) participated in one scan. Blood samples were collected for DNA analysis and genotyped for single nucleotide polymorphisms (SNPs) in the CHRNA4 and ANKK1 gene loci. β2*-nAChR availability was measured in the thalamus, striatum, cortical regions, and cerebellum. RESULTS The CHRNA4 SNP rs2236196 and ANKK1 SNP rs4938015 were associated with significantly higher cerebellar and cortical β2*-nAChR availability in smokers versus nonsmokers for specific genotypes. There were no significant differences by carrier status in the change in β2*-nAChR availability in smokers from 7-9 days to 6-8 weeks of abstinence. CONCLUSION This study provides evidence for genetic regulation of tobacco smoking-induced changes in β2*-nAChR availability and suggests that β2*-nAChR availability could be an endophenotype mediating influences of CHRNA4 variants on nicotine dependence. These results highlight individual differences in the neurochemistry of nicotine dependence and may suggest the need for individualized programs for smoking cessation. IMPLICATIONS This study demonstrates genetic regulation of smoking-induced changes in β2*-nAChRs throughout the brain and highlights the need for personalized programs for smoking cessation.
- Subjects :
- Adult
Male
medicine.medical_specialty
media_common.quotation_subject
medicine.medical_treatment
Single-nucleotide polymorphism
Smoking Prevention
Protein Serine-Threonine Kinases
Receptors, Nicotinic
Polymorphism, Single Nucleotide
White People
Iodine Radioisotopes
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Humans
Neurochemistry
media_common
Original Investigation
Tomography, Emission-Computed, Single-Photon
ANKK1
business.industry
Smoking
Public Health, Environmental and Occupational Health
Tobacco Use Disorder
Abstinence
Corpus Striatum
030227 psychiatry
Up-Regulation
Nicotinic acetylcholine receptor
Endocrinology
Nicotinic agonist
Endophenotype
Case-Control Studies
Smoking cessation
Female
Smoking Cessation
sense organs
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....ba827fd7823f55f7abb11f0315d728e3