Chrna5, encoding the α5 subunit of the nicotinic acetylcholine receptor (nAChR), is a key component of nAChRs. These receptors are ligand-gated ion channels that play a role in neurotransmission, with the cholinergic system they belong to being involved in processes like reward and addiction vulnerability [2,4].

Genetic variation in CHRNA5 has been associated with multiple diseases. In European populations, the rs16969968 polymorphism in CHRNA5 is linked to an increased risk of lung cancer, while no such association is seen in Asians. The minor allele A may increase lung cancer risk in both smokers and non-smokers [1]. The rs16969968 allele (A) is also associated with a lower likelihood of smoking cessation, and the AA genotype is related to a delay in the median age of quitting and an earlier median age of lung cancer diagnosis in smokers [3]. Moreover, in mouse models, Chrna5-knockout significantly reduced the severity of psoriasis-like inflammation in imiquimod-induced mouse models, regulating inflammation through the MAPK kinase kinase-1/c-Jun N-terminal kinase‒MAPK/NF-κB pathway [5].

In conclusion, Chrna5 is crucial for the function of nAChRs and is involved in the cholinergic system. Model-based research, especially the Chrna5-knockout mouse model, has revealed its role in diseases such as lung cancer, smoking-related behaviors, and psoriasis, providing insights into the underlying mechanisms and potential therapeutic targets for these conditions [1,3,5].

References:

1. Zhou, Wei, Zhu, Wenjie, Tong, Xunliang, Li, Yi, Li, Yanming. 2020. CHRNA5 rs16969968 polymorphism is associated with lung cancer risk: A meta-analysis. In The clinical respiratory journal, 14, 505-513. doi:10.1111/crj.13165. https://pubmed.ncbi.nlm.nih.gov/32049419/

2. Brynildsen, Julia K, Blendy, Julie A. 2021. Linking the CHRNA5 SNP to drug abuse liability: From circuitry to cellular mechanisms. In Neuropharmacology, 186, 108480. doi:10.1016/j.neuropharm.2021.108480. https://pubmed.ncbi.nlm.nih.gov/33539855/

3. Chen, Li-Shiun, Hung, Rayjean J, Baker, Timothy, Amos, Christopher I, Bierut, Laura J. 2015. CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis. In Journal of the National Cancer Institute, 107, . doi:10.1093/jnci/djv100. https://pubmed.ncbi.nlm.nih.gov/25873736/

4. Picciotto, Marina R, Kenny, Paul J. 2021. Mechanisms of Nicotine Addiction. In Cold Spring Harbor perspectives in medicine, 11, . doi:10.1101/cshperspect.a039610. https://pubmed.ncbi.nlm.nih.gov/32341069/

5. Wang, Jing, Li, Xiangying, Zhang, Ping, Huang, Shuhong, Dang, Ningning. 2022. CHRNA5 Is Overexpressed in Patients with Psoriasis and Promotes Psoriasis-Like Inflammation in Mouse Models. In The Journal of investigative dermatology, 142, 2978-2987.e6. doi:10.1016/j.jid.2022.04.014. https://pubmed.ncbi.nlm.nih.gov/35513071/