China
Africa
Explore chapters and articles related to this topic
A Genetic Framework for Addiction
Published in Hanna Pickard, Serge H. Ahmed, The Routledge Handbook of Philosophy and Science of Addiction, 2019
Philip Gorwood, Yann Le Strat, Nicolas Ramoz
According to the World Health Organization (WHO), the total of tobacco consumers is 1.3 billion people leading to approximately 5 million deaths per year. In 2007, the first large-scale genetic analysis on nicotine dependence was carried out on 348 candidate genes, by genotyping 3,713 SNPs in 1,050 patients addicted to tobacco and 879 non-dependent smoker subjects (Saccone 2007). This study showed variants associated with nicotine dependence in the cluster of the genes CHRNA3, CHRNA5 and CHRNB4 coding respectively the subunits α3, α3 and β4, involved in the formation of nicotinic heteromeric receptors in acetylcholine (Figure 22.3).
The Etiology of Addiction
Published in James MacKillop, George A. Kenna, Lorenzo Leggio, Lara A. Ray, Integrating Psychological and Pharmacological Treatments for Addictive Disorders, 2017
These studies make it clear that genetic variation is an important influence on the development of addiction, but the mechanisms by which this influence is conferred have been elusive. Candidate gene studies have generated mixed findings and atheoretical genome-wide association studies have generally not identified significant loci. However, two notable exceptions are robust evidence that variation in a locus responsible for alcohol pharma cokinetics is a protective factor against alcohol use disorder, and that variation putatively related to nicotine pharmacodynamics is a risk factor for nicotine dependence. In the first case, the ALHD2 gene is responsible for aldehyde dehydrogenase activity, a key enzyme for breaking down acetaldehyde resulting from alcohol metabolism, and the A allele of an SNP (rs671) within ALDH2 results in substantially lower enzymatic activity. As a result, if A allele carriers drink alcohol, they experience an acetaldehyde buildup and a number of unpleasant symptoms, including flushing, nausea, headache, and tachycardia. The A allele is relatively common in Asian populations and effectively makes carriers “allergic” to alcohol, exerting a powerful protective effect against alcohol use disorder [26]. In the second case, a number of large-scale studies have convincingly implicated variants on chromosome 15 with nicotine dependence. This region contains the α5-α3-β4 nicotinic receptor gene cluster, and nicotinic cholinergic receptors are key sites of action for nicotine. In particular, a locus in the α5 nicotinic receptor subunit gene (Chrna5), rs16969968, has been associated with significantly increased risk for developing nicotine dependence and smoking-related diseases, such as lung cancer and chronic obstructive pulmonary disease [27].
A review on the reciprocal interactions between neuroinflammatory processes and substance use and misuse, with a focus on alcohol misuse
Published in The American Journal of Drug and Alcohol Abuse, 2023
Anny Gano, Terrence Deak, Ricardo Marcos Pautassi
Several studies have analyzed genetic mechanisms implicating inflammatory processes in the expression of SUDs. Most of these focused on AUD and on liver conditions secondary to alcohol use, such as liver disease induced by alcohol use. These studies provided conclusive evidence for a role of genetic variants in the disease severity or prognosis (61). Likewise, it has been shown that only 10–20% of smokers develop chronic obstructive pulmonary disease, a condition featuring chronic inflammatory response in the lung that are associated with severe changes in lung physiology. Those smokers susceptible to develop chronic obstructive pulmonary disease, however, exhibited genetic variants in several genes, such as IL6R and TNF. Notably, some of those genes (e.g., CHRNA5/3) also provide susceptibility for nicotine use disorders [reviewed in (62)]
Biologic insights from single-cell studies of psoriasis and psoriatic arthritis
Published in Expert Opinion on Biological Therapy, 2022
Joy Q Jin, David Wu, Riley Spencer, Kareem G Elhage, Jared Liu, Mitchell Davis, Marwa Hakimi, Sugandh Kumar, Zhi-Ming Huang, Tina Bhutani, Wilson Liao
Other potential diagnostic biomarkers and therapeutic targets among keratinocytes were identified via scRNA-seq in two studies. Zhou et al. found PSO lesions to exhibit downregulated PERP, a component of intercellular desmosomes highly expressed in keratinocytes, which was associated with weakened cell–cell adhesion and wound healing [28]. In another investigation, CHRNA5 was shown to be highly expressed in PSO lesions, with Chrna5 knockout mice exhibiting significantly reduced PSO severity [41]. CHRNA5 likely mediates inflammation through the MAPKK1/c-Jun/NFκB pathway, as scRNA-seq data showed significantly decreased proportions of keratinocyte subpopulations and decreased JAK/STAT signaling in mice. Silencing of CHRNA5 also led to inhibition of keratinocyte proliferation and migration.
Molecular links between COPD and lung cancer: new targets for drug discovery?
Published in Expert Opinion on Therapeutic Targets, 2019
Gaetano Caramori, Paolo Ruggeri, Sharon Mumby, Antonio Ieni, Federica Lo Bello, Vrushali Chaminka, Chantal Donovan, Filippo Andò, Francesco Nucera, Irene Coppolino, Giovanni Tuccari, Philip M. Hansbro, Ian M. Adcock
Two single-nucleotide polymorphisms (SNPs) in chromosome 15 (15q25.1) are associated with lung cancer risk. This region contains a cluster of six genes: nicotinic acetylcholine receptor alpha subunits 3 (CHRNA3) and 5 (CHRNA5), the β4 nicotinic acetylcholine receptor (nAChR) subunit (CHRNB4), proteasome alpha 4 subunit isoform 1 (PMSA4), the IREB2 iron-sensing response element, and LOC123688, a gene of unknown function [33]. Fourteen percent of lung cancer risk is associated with this region with the strongest association with rs16969968 in exon 5 of CHRNA5 that induces an amino acid substitution (D398N). The functional effect of this substitution is unknown [33]. A synonymous variant in exon 5 (rs1051730) of CHRNA3 is also strongly associated with lung cancer. There is a fivefold greater risk of lung cancer in subjects who have both a family history of lung cancer and two copies of the high-risk alleles rs8034191 (odds ratio [OR] = 7.20) or rs1051730 (OR = 5.67), which are located in the 15q24-25.1 locus [34].