Slc22a2-KO Mouse

Slc22a2, encoding the organic cation transporter-2 (OCT2), is a member of the SLC22 transporter family. It mediates the electrogenic transport of small organic cations with different molecular structures, playing a role in the uptake, pharmacological effects, and/or adverse effects of many cationic clinical therapeutics and xenobiotics [3,7]. It is also involved in key metabolic pathways and levels of signaling molecules, and is responsible for about 80% of the total metformin clearance [3,4].

In patients with colorectal cancer receiving oxaliplatin chemotherapy, the rs316019 genotype of Slc22a2 was significantly associated with the severity of leucopenia and neutropenia, and the rs1869641 genotype was associated with the occurrence of thrombocytopenia [1]. In HIV-positive patients treated with dolutegravir, the SLC22A2 CA genotype was associated with abnormal general severity index, anxiety, hostility, and moderate to severe headache [2]. Variants in Slc22a2 were associated with phenotypes of net tubular creatinine secretion and end-stage renal disease in renal transplant recipients [5]. Also, the SLC22A2 808G/G genotype, among other factors, influenced the change rate of creatinine in chronic myeloid leukemia patients taking bosutinib [6].

In conclusion, Slc22a2 is crucial for drug transport and metabolic regulation. Studies on its genetic polymorphisms in various patient populations have revealed its associations with drug-related hematological toxicities, psychiatric symptoms, creatinine-related phenotypes, and more. These findings contribute to understanding the role of Slc22a2 in different disease conditions and drug responses.

References:

1. Chen, Jiayin, Wang, Li, Tong, Gangling, Liu, Chaoran, Wang, Lijun. . The SLC22A2 gene is a determinant of hematological toxicity of oxaliplatin in patients with colorectal cancer. In International journal of clinical pharmacology and therapeutics, 61, 1-7. doi:10.5414/CP204156. https://pubmed.ncbi.nlm.nih.gov/36331012/

2. Borghetti, A, Calcagno, A, Lombardi, F, Bonora, S, Di Giambenedetto, S. . SLC22A2 variants and dolutegravir levels correlate with psychiatric symptoms in persons with HIV. In The Journal of antimicrobial chemotherapy, 74, 1035-1043. doi:10.1093/jac/dky508. https://pubmed.ncbi.nlm.nih.gov/30561642/

3. Pearce, Brendon, Jacobs, Clifford, Hoosain, Nisreen, Benjeddou, Mongi. . SLC22A2 - mapping genomic variations within South African indigenous and admixed populations. In Drug metabolism and personalized therapy, 31, 213-220. doi:10.1515/dmpt-2016-0022. https://pubmed.ncbi.nlm.nih.gov/27828777/

4. Nigam, Sanjay K. . The SLC22 Transporter Family: A Paradigm for the Impact of Drug Transporters on Metabolic Pathways, Signaling, and Disease. In Annual review of pharmacology and toxicology, 58, 663-687. doi:10.1146/annurev-pharmtox-010617-052713. https://pubmed.ncbi.nlm.nih.gov/29309257/

5. Reznichenko, Anna, Sinkeler, Steef J, Snieder, Harold, Seelen, Marc, Navis, Gerjan. 2013. SLC22A2 is associated with tubular creatinine secretion and bias of estimated GFR in renal transplantation. In Physiological genomics, 45, 201-9. doi:10.1152/physiolgenomics.00087.2012. https://pubmed.ncbi.nlm.nih.gov/23341218/

6. Abumiya, Maiko, Takahashi, Naoto, Takahashi, Saori, Kameoka, Yoshihiro, Miura, Masatomo. 2021. Effects of SLC22A2 808G>T polymorphism and bosutinib concentrations on serum creatinine in patients with chronic myeloid leukemia receiving bosutinib therapy. In Scientific reports, 11, 6362. doi:10.1038/s41598-021-85757-7. https://pubmed.ncbi.nlm.nih.gov/33737618/

7. Jacobs, Clifford, Pearce, Brendon, Du Plessis, Mornè, Hoosain, Nisreen, Benjeddou, Mongi. 2015. Single nucleotide polymorphisms of the SLC22A2 gene within the Xhosa population of South Africa. In Drug metabolism and pharmacokinetics, 30, 457-60. doi:10.1016/j.dmpk.2015.11.002. https://pubmed.ncbi.nlm.nih.gov/26674735/