Slc22a1-KO Mouse

Slc22a1, also known as the gene encoding the organic cation transporter 1 (hOCT1), is a crucial gene. hOCT1 is expressed in epithelial barriers and various drug-target cells. It significantly contributes to drug pharmacokinetics by mediating the translocation of numerous drugs, and may also play a role in pharmacodynamics [2]. It is involved in the substance transport of hepatocytes and has been associated with multiple physiological processes and disease-related pathways [3]. Genetic models, especially those studying its polymorphisms, are valuable for understanding its function in drug response and disease [1,2,4,5].

The SLC22A1 rs628031A or rs683369G allele carriers had a lower major molecular response rate in imatinib-treated chronic myeloid leukemia patients, indicating its role in drug response [1]. SLC22A1 polymorphisms influence metformin pharmacokinetics and HbA1c levels, such as rs12208357, rs34059508, and G465R affecting metformin plasma levels, and rs628031, rs622342 etc. influencing HbA1c [4]. SLC22A1 rs34059508 G/A genotype was associated with higher dose/weight-corrected area under the curve of amlodipine and related to thoracic pain and dizziness, showing its impact on amlodipine pharmacokinetics and safety [5]. Also, the SLC22A1 variant was associated with a higher risk of severe infectious toxicity in children with acute lymphoblastic leukemia [6].

In conclusion, Slc22a1, through its encoded hOCT1, is vital in drug-related processes, influencing the pharmacokinetics and efficacy of drugs like imatinib, metformin, and amlodipine. It also has implications in diseases such as chronic myeloid leukemia, diabetes, and acute lymphoblastic leukemia. The study of Slc22a1 polymorphisms using genetic models helps to understand its role in these disease areas and drug responses, providing insights for personalized medicine.

References:

1. Cargnin, Sarah, Ravegnini, Gloria, Soverini, Simona, Angelini, Sabrina, Terrazzino, Salvatore. 2018. Impact of SLC22A1 and CYP3A5 genotypes on imatinib response in chronic myeloid leukemia: A systematic review and meta-analysis. In Pharmacological research, 131, 244-254. doi:10.1016/j.phrs.2018.02.005. https://pubmed.ncbi.nlm.nih.gov/29427770/

2. Arimany-Nardi, C, Koepsell, H, Pastor-Anglada, M. 2015. Role of SLC22A1 polymorphic variants in drug disposition, therapeutic responses, and drug-drug interactions. In The pharmacogenomics journal, 15, 473-87. doi:10.1038/tpj.2015.78. https://pubmed.ncbi.nlm.nih.gov/26526073/

3. Yu, Huiying, Li, Bin, Guo, Huili, Pang, Xiuqing, Gao, Zhiliang. 2025. SLC22A1 resists HBV by activating JAK/STAT pathway and predicts effect of pegIFNα-based therapy on CHB. In The Journal of infectious diseases, , . doi:10.1093/infdis/jiaf102. https://pubmed.ncbi.nlm.nih.gov/40036258/

4. Pradana, A D, Kristin, E, Nugrahaningsih, D A A, Nugroho, A K, Pinzon, R T. . Influence of Solute Carrier Family 22 Member 1 (SLC22A1) Gene Polymorphism on Metformin Pharmacokinetics and HbA1c Levels: A Systematic Review. In Current diabetes reviews, 20, e070823219470. doi:10.2174/1573399820666230807145202. https://pubmed.ncbi.nlm.nih.gov/37550919/

5. Soria-Chacartegui, Paula, Zubiaur, Pablo, Ochoa, Dolores, Martín-Vilchez, Samuel, Abad-Santos, Francisco. 2023. Genetic Variation in CYP2D6 and SLC22A1 Affects Amlodipine Pharmacokinetics and Safety. In Pharmaceutics, 15, . doi:10.3390/pharmaceutics15020404. https://pubmed.ncbi.nlm.nih.gov/36839726/

6. Fernandes, Sweny de S M, Leitão, Luciana P C, Cohen-Paes, Amanda de N, Santos, Sidney E B Dos, Santos, Ney P C Dos. 2022. The Role of SLC22A1 and Genomic Ancestry on Toxicity during Treatment in Children with Acute Lymphoblastic Leukemia of the Amazon Region. In Genes, 13, . doi:10.3390/genes13040610. https://pubmed.ncbi.nlm.nih.gov/35456416/