Slc22a2-KO Mouse

Slc22a2, encoding the organic cation transporter-2 (OCT2), is a polyspecific transporter in the SLC22 transporter family [3,4]. It mediates the electrogenic transport of small organic cations with different molecular structures, playing a role in drug transport, and is responsible for about 80% of the total metformin clearance [3]. It also impacts key metabolic pathways and signaling molecule levels, and is involved in interorgan and inter-organism small-molecule communication [4].

In colorectal cancer patients, certain single-nucleotide polymorphisms (SNPs) of Slc22a2 are associated with the hematological toxicity of oxaliplatin. For example, rs1869641 genotype is related to the occurrence of thrombocytopenia, and rs316019 genotype is associated with the severity of leucopenia and neutropenia [1]. In HIV-positive patients on dolutegravir-containing regimens, the SLC22A2 CA genotype is associated with abnormal general severity index, anxiety, hostility, and moderate to severe headache [2]. In renal transplantation, SLC22A2 polymorphisms are associated with phenotypes of net tubular creatinine secretion and end-stage renal disease (ESRD) [5].

In conclusion, Slc22a2 is crucial for drug transport and has implications in multiple disease areas. Its role in drug-related toxicities in cancer chemotherapy, psychiatric symptoms in HIV patients, and renal-related phenotypes and diseases has been revealed through human-based studies. Understanding Slc22a2 provides insights into disease mechanisms and may guide more personalized treatment strategies.

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/