Adra2c, encoding the α2C-adrenergic receptor, is involved in adrenergic receptor signaling pathways. It plays a role in modulating epinephrine release from the adrenals in mice, being associated with the fight-or-flight response [3]. This receptor can also affect other physiological processes through its associated signaling cascades, and its expression is regulated by epigenetic mechanisms such as histone methylation and acetylation [1].

In the context of diseases, Adra2c has been implicated in multiple conditions. In schizophrenia, its mRNA expression is upregulated in all schizophrenia subjects regardless of antipsychotic treatment [1]. In pheochromocytoma-induced cardiomyopathy, the variant in Adra2c (alpha 2CDel322-325) was more common among patients with catecholamine-induced cardiomyopathy, and the lack of this polymorphism has a high negative predictive value for the onset of the disease [5]. In ST-segment-elevation myocardial infarction, the ADRA2C 322-325 deletion carriers were associated with a reduced incidence of ventricular fibrillation [6]. In addition, its expression may be associated with glioma cell migration, apoptosis, and invasion, and it could serve as a biomarker or target for cancer diagnosis, prognosis, and treatment, especially for glioblastoma multiforme [2]. Also, in chicken domestication, although initially proposed as an important gene due to a selective sweep near it, further studies did not find it to be involved in the domestication of the stress response [3]. In recurrent implantation failure, patients show attenuated expression of ADRA2C, and its down-regulation induced by high-level epinephrine can inhibit decidualization [4].

In conclusion, Adra2c is a crucial gene involved in adrenergic receptor signaling with implications in various diseases such as schizophrenia, cardiomyopathy, myocardial infarction, cancer, and pregnancy-related disorders. While genetic models were not prominently featured in the references, the studies on human subjects have provided valuable insights into its role in these disease conditions, highlighting its potential as a biomarker or therapeutic target.

References:

1. Brocos-Mosquera, Iria, Miranda-Azpiazu, Patricia, Muguruza, Carolina, Callado, Luis F, Rivero, Guadalupe. 2021. Differential brain ADRA2A and ADRA2C gene expression and epigenetic regulation in schizophrenia. Effect of antipsychotic drug treatment. In Translational psychiatry, 11, 643. doi:10.1038/s41398-021-01762-4. https://pubmed.ncbi.nlm.nih.gov/34930904/

2. Zhang, Xiaoxiao, Chen, Huitong, Wang, Chenyang, Huang, Ning, Chen, Junli. 2024. Pan-cancer analysis of the role of α2C-adrenergic receptor (ADRA2C) in human tumors and validation in glioblastoma multiforme models. In Journal of Cancer, 15, 5691-5709. doi:10.7150/jca.98240. https://pubmed.ncbi.nlm.nih.gov/39308687/

3. Elfwing, Magnus, Fallahshahroudi, Amir, Lindgren, Isa, Jensen, Per, Altimiras, Jordi. 2014. The strong selective sweep candidate gene ADRA2C does not explain domestication related changes in the stress response of chickens. In PloS one, 9, e103218. doi:10.1371/journal.pone.0103218. https://pubmed.ncbi.nlm.nih.gov/25111139/

4. Wu, Jinxiang, Lin, Shu, Huang, Pinxiu, Wang, Haibin, Kong, Shuangbo. 2022. Maternal anxiety affects embryo implantation via impairing adrenergic receptor signaling in decidual cells. In Communications biology, 5, 840. doi:10.1038/s42003-022-03694-1. https://pubmed.ncbi.nlm.nih.gov/35982177/

5. Amar, Jacques, Brunel, Jeremy, Cardot Bauters, Catherine, Odou, Marie-Françoise, Savagner, Frédérique. 2022. Genetic biomarkers of life-threatening pheochromocytoma-induced cardiomyopathy. In Endocrine-related cancer, 29, 267-272. doi:10.1530/ERC-21-0373. https://pubmed.ncbi.nlm.nih.gov/35258481/

6. Chevalier, Philippe, Roy, Pascal, Bessière, Francis, Carroll, Ian A, Bristow, Michael R. 2023. Impact of Neuroeffector Adrenergic Receptor Polymorphisms on Incident Ventricular Fibrillation During Acute Myocardial Ischemia. In Journal of the American Heart Association, 12, e025368. doi:10.1161/JAHA.122.025368. https://pubmed.ncbi.nlm.nih.gov/36926933/