GNB3, encoding the G-protein β3 subunit, is involved in transmitting signals from the cell surface to intracellular signal cascades. The protein it encodes is widely expressed, participating in various physiological and pathophysiological processes [6]. Genetic polymorphisms, like the C825T polymorphism, have been studied to understand its role in different biological contexts [1-6, 8-10].

A meta-analysis of eight studies showed that the GNB3 C825T polymorphism was associated with an increased risk of pre-eclampsia in the recessive model, and subgroup analysis also revealed associations in other genetic models [1]. In major depressive disorder, the C825T polymorphism was significantly correlated with a higher response rate to antidepressants in the allele and dominant models, especially among Asians [2]. In renal allograft recipients, the homozygous GNB3 TT genotype was associated with a higher frequency of death due to acute cardiovascular events, and lower rates of myocardial infarction-free and acute peripheral artery occlusive disease-free survival [3]. GNB3 overexpression in transgenic mice led to increased adiposity, metabolic syndrome-related symptoms like elevated fasting plasma glucose, insulin, and dysregulation of acute thermogenesis [4]. The GNB3 rs5443 TT genotype was associated with protection against COVID-19 fatality and higher SARS-CoV-2-specific T cell responses [5]. No significant association was found between GNB3 rs5443 polymorphism and endurance athlete status [7]. CC genotype carriers of GNB3 c.825C>T polymorphism had an increased T-cell immune response to SARS-CoV-2 after mRNA-1273 vaccination [8].

In conclusion, GNB3 is crucial in signal transduction and is involved in multiple disease-related processes such as pre-eclampsia, major depressive disorder, cardiovascular events post-renal transplant, obesity, metabolic syndrome, COVID-19 outcomes, and immune responses to vaccination. These findings from human genetic association studies and animal models help to understand the biological functions of GNB3 and its potential implications in disease diagnosis, treatment, and prevention.

References:

1. Song, Jiajia, Huang, Xianping, Zhou, Panpan, Xu, Ting, Xu, Zhangye. 2021. Meta-analysis of the genetic association between maternal GNB3 C825T polymorphism and risk of pre-eclampsia. In International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 154, 385-392. doi:10.1002/ijgo.13560. https://pubmed.ncbi.nlm.nih.gov/33368205/

2. Hu, Qiang, Zhang, Sheng-Yu, Liu, Fei, Wei, Dong-Mei, Zang, Yin-Yin. 2014. Influence of GNB3 C825T polymorphism on the efficacy of antidepressants in the treatment of major depressive disorder: A meta-analysis. In Journal of affective disorders, 172, 103-9. doi:10.1016/j.jad.2014.09.039. https://pubmed.ncbi.nlm.nih.gov/25451402/

3. Peitz, Tobias, Möhlendick, Birte, Siffert, Winfried, Eisenberger, Ute, Friebus-Kardash, Justa. 2022. GNB3 c.825C>T (rs5443) Polymorphism and Risk of Acute Cardiovascular Events after Renal Allograft Transplant. In International journal of molecular sciences, 23, . doi:10.3390/ijms23179783. https://pubmed.ncbi.nlm.nih.gov/36077181/

4. Ozdemir, Alev Cagla, Wynn, Grace M, Vester, Aimee, Srinivasan, Shanthi, Rudd, M Katharine. 2017. GNB3 overexpression causes obesity and metabolic syndrome. In PloS one, 12, e0188763. doi:10.1371/journal.pone.0188763. https://pubmed.ncbi.nlm.nih.gov/29206867/

5. Möhlendick, Birte, Schönfelder, Kristina, Zacher, Christoph, Jöckel, Karl-Heinz, Siffert, Winfried. 2022. The GNB3 c.825C>T (rs5443) polymorphism and protection against fatal outcome of corona virus disease 2019 (COVID-19). In Frontiers in genetics, 13, 960731. doi:10.3389/fgene.2022.960731. https://pubmed.ncbi.nlm.nih.gov/36017493/

6. Klenke, Stefanie, Kussmann, Martin, Siffert, Winfried. . The GNB3 C825T polymorphism as a pharmacogenetic marker in the treatment of hypertension, obesity, and depression. In Pharmacogenetics and genomics, 21, 594-606. doi:10.1097/FPC.0b013e3283491153. https://pubmed.ncbi.nlm.nih.gov/21709600/

7. İpekoğlu, Gökhan, Apaydın, Necdet, Çetin, Tuğba, Civelek, Güngör, Sakar, Mert. 2024. Examining the relationship between genetic polymorphisms (BDKRB2, GNB3, HIF1A, MCT1, NOS3) and endurance athlete status. In European journal of applied physiology, 124, 1943-1958. doi:10.1007/s00421-024-05498-z. https://pubmed.ncbi.nlm.nih.gov/38753016/

8. Čiučiulkaitė, Ieva, Möhlendick, Birte, Thümmler, Laura, Siffert, Winfried, Lindemann, Monika. 2022. GNB3 c.825c>T polymorphism influences T-cell but not antibody response following vaccination with the mRNA-1273 vaccine. In Frontiers in genetics, 13, 932043. doi:10.3389/fgene.2022.932043. https://pubmed.ncbi.nlm.nih.gov/36105097/