ArticleMolecular pharmacology2011
Acetylcholine receptor (AChR) α5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (α4β2)₂α5 AChR function.
Article in Molecular pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
132 citing papers in PubMed, 5 syntheses or guidelines pooled it, 166 citations in OpenAlex.
- Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-Analysis.EBioMedicine · 2016Pooled it
- Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.Molecular psychiatry · 2016Pooled it
- CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis.Journal of the National Cancer Institute · 2015Pooled it
- Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking.Genetic epidemiology · 2013Pooled it
- Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.Archives of general psychiatry · 2012Pooled it
- Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Trial
- Smoking cessation pharmacogenetics: analysis of varenicline and bupropion in placebo-controlled clinical trials.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Trial
- A new framework for nicotinic receptor-targeted therapeutic strategies in psychiatric and neurodegenerative disorders.Frontiers in cellular neuroscience · 2026Article
- Nicotinic Receptors in the Medial Habenula to Interpeduncular Nucleus Pathway: Modulators of Reward, Aversion and Emotion.The European journal of neuroscience · 2025Review
- Ion channel mutations and cancer.Biochemistry and biophysics reports · 2025Review
- Linking altered neuronal and synaptic properties to nicotinic receptor Alpha5 subunit gene dysfunction: a translational investigation in rat mPFC and human cortical layer 6.Translational psychiatry · 2025Article
- Distinct Chrna5 mutations link excessive alcohol use to types I/II vulnerability profiles and IPN GABAergic neurons.Translational psychiatry · 2024Article
- Smoking-Related Increases in Alcohol Outcomes and Preliminary Evidence for the Protective Effect of a Functional Nicotine Receptor Gene (CHRNA5) Variant on Alcohol Consumption in Individuals Without Alcohol Use Disorder.The international journal of neuropsychopharmacology · 2024Article
- Nicotinic Receptor Alpha-5 Subunit Gene Polymorphism is Associated With Heavy Smoking Under a Range of Nicotine Dosing Conditions.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Article
- CHRNA5 links chandelier cells to severity of amyloid pathology in aging and Alzheimer's disease.Translational psychiatry · 2024Article
- The many enigmas of nicotine.Advances in pharmacology (San Diego, Calif.) · 2024Review
- CHRNA5 gene variation affects the response of VTA dopaminergic neurons during chronic nicotine exposure and withdrawal.Neuropharmacology · 2023Article
- Synthesis and Biological Activity of Novel α-Conotoxins Derived from Endemic Polynesian Cone Snails.Marine drugs · 2023Article
- Gene-environment interaction explains a part of missing heritability in human body mass index.Communications biology · 2023Article
- A common SNP in Chrna5 enhances morphine reward in female mice.Neuropharmacology · 2022Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Genomic studies have identified a D398N variation in the α5 subunit of nicotinic acetylcholine receptors (AChRs) that increases risk of nicotine dependence and lung cancer. (α4β2)₂α5 AChRs are a significant brain presynaptic subtype in brain. Their high sensitivity to activation by nicotine and high Ca²+ permeability give them substantial functional impact. α3β4* and α3β2* AChRs are predominant postsynaptic AChRs in the autonomic nervous system, but rare in brain. The amino acid 398 of α5 is located in the large cytoplasmic domain near the amphipathic α helix preceding the M4 transmembrane domain. These helices have been shown to influence AChR conductance by forming portals to the central channel. We report that α5 Asn 398 lowers Ca²+ permeability and increases short-term desensitization in (α4β2)₂α5 but not in (α3β4)₂α5 or (α3β2)₂α5 AChRs. This suggests that a positive allosteric modulator would augment nicotine replacement therapy for those with this risk variant. α5 D398N variation does not alter sensitivity to activation. The high sensitivity to activation and desensitization of (α4β2)₂α5 AChRs by nicotine results in a narrow concentration range in which activation and desensitization curves overlap. This region centers on 0.2 μM nicotine, a concentration typically sustained in smokers. This concentration would desensitize 60% of these AChRs and permit smoldering activation of the remainder. The low sensitivity to activation and desensitization of (α3β4)₂α5 AChRs by nicotine results in a broad region of overlap centered near 10 μM. Thus, at the nicotine concentrations in smokers, negligible activation or desensitization of this subtype would occur.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.