Slc28a2, also known as human concentrative nucleoside transporter 2 (hCNT2), is a key gene encoding a protein involved in the transmembrane transport of nucleosides. It plays a major role in the intestinal absorption of natural nucleosides and some nucleoside analog drugs. The gene is part of the solute carrier 28 family, and its function is crucial for the body's nucleotide metabolism and drug disposition processes [4,5,6].

In rectal cancer, high SLC28A2 immunoexpression is significantly associated with an advanced stage, poor response to neoadjuvant concurrent chemoradiotherapy (CCRT), and worse patient survival, suggesting it can be a valuable predictive and prognostic marker [1]. In hepatitis C treatment, the SLC28A2 rs11854484 TT genotype is independently associated with clinically significant anaemia in patients receiving triple therapy, helping to identify a subgroup of patients with better tolerance of the treatment [3]. Also, common variants in the SLC28A2 gene are associated with serum uric acid level, hyperuricemia, and gout in Han Chinese [2].

In conclusion, Slc28a2 is essential for nucleoside transport, which has implications for normal physiological functions and drug responses. Its role in diseases such as rectal cancer, hepatitis C-related anaemia, and gout-related conditions, as revealed through various studies, highlights its importance in understanding disease mechanisms and potentially developing targeted therapies.

References:

1. Chen, Hsin-Pao, Chen, Chih-I, Liu, Kuang-Wen, Chou, Chia-Lin, Lai, Hong-Yue. 2022. High SLC28A2 expression endows an inferior survival for rectal cancer patients managed by neoadjuvant CCRT. In Pathology, research and practice, 239, 154158. doi:10.1016/j.prp.2022.154158. https://pubmed.ncbi.nlm.nih.gov/36244249/

2. Zhou, Zhaowei, Li, Zhiqiang, Wang, Can, Li, Changgui, Shi, Yongyong. 2019. Common variants in the SLC28A2 gene are associated with serum uric acid level and hyperuricemia and gout in Han Chinese. In Hereditas, 156, 4. doi:10.1186/s41065-018-0078-0. https://pubmed.ncbi.nlm.nih.gov/30679935/

3. Ampuero, Javier, Del Campo, José Antonio, Rojas, Lourdes, Millán, Raquel, Romero-Gómez, Manuel. 2015. Role of ITPA and SLC28A2 genes in the prediction of anaemia associated with protease inhibitor plus ribavirin and peginterferon in hepatitis C treatment. In Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 68, 56-60. doi:10.1016/j.jcv.2015.05.010. https://pubmed.ncbi.nlm.nih.gov/26071337/

4. Li, Linghui, Koo, Seok Hwee, Hong, Ivan Hee Kean, Lee, Edmund Jon Deoon. . Identification of functional promoter haplotypes of human concentrative nucleoside transporter 2, hCNT2 (SLC28A2). In Drug metabolism and pharmacokinetics, 24, 161-6. doi:. https://pubmed.ncbi.nlm.nih.gov/19430172/

5. Yee, Sook Wah, Shima, James E, Hesselson, Stephanie, Ahituv, Nadav, Giacomini, Kathleen M. 2008. Identification and characterization of proximal promoter polymorphisms in the human concentrative nucleoside transporter 2 (SLC28A2). In The Journal of pharmacology and experimental therapeutics, 328, 699-707. doi:10.1124/jpet.108.147207. https://pubmed.ncbi.nlm.nih.gov/19098160/

6. Elwi, Adam N, Damaraju, Vijaya L, Baldwin, Stephen A, Sawyer, Michael B, Cass, Carol E. . Renal nucleoside transporters: physiological and clinical implications. In Biochemistry and cell biology = Biochimie et biologie cellulaire, 84, 844-58. doi:. https://pubmed.ncbi.nlm.nih.gov/17215872/