General Information of Drug Transporter (DT)
DT ID	DTD0245 Transporter Info
Gene Name	SLC28A2
Protein Name	Concentrative nucleoside transporter 2
Gene ID	9153
UniProt ID	O43868
Genetic Polymorphisms of DT (GPD)
Genetic Polymorphism	rs1060896
Site of GPD	chr15:45262069 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	C>A
Minor Allele Frequency	A=0.3131/1568 (Global)
Genotype AA	Click to Show/Hide the Full List of Affected Drugs:           4 Drugs in Total
Gemcitabine	Drug Info	Pancreatic Neoplasm	Irrelevant to the increased drug response in patients (compare with genotypes AC + CC)		[ 1]
Gemcitabine	N.A.	Neutropenia	Genotype AA is not associated with increased response to gemcitabine in people with Pancreatic Neoplasms as compared to genotypes AC + CC.		[ 1]
Gemcitabine	N.A.	Neoplasms	Genotype AA is not associated with increased response to gemcitabine in people with Pancreatic Neoplasms as compared to genotypes AC + CC.		[ 1]
Gemcitabine	N.A.	Neoplasms	Patients with the AA genotype and cancer may have increased survival time and an increased risk for hematologic toxicity when treated with gemcitabine as compared to patients with the CC genotype. Other genetic and clinical factors may also influence toxicity and response in patients receiving gemcitabine.		[ 2]
Genotype CC	Click to Show/Hide the Full List of Affected Drugs:           3 Drugs in Total
Gemcitabine	Drug Info	Non-Small-Cell Lung Carcinoma	Correlated with the decreased drug response in patients (compare with genotypes AA + AC); Correlated with the decreased hematologic toxicity risk in patients (compare with genotypes AA + AC)		[ 2]
Gemcitabine	N.A.	Neutropenia	Genotype CC is associated with decreased risk of hematologic toxicity when treated with gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes AA + AC.		[ 2]
Gemcitabine	N.A.	Neoplasms	Genotype CC is associated with decreased risk of hematologic toxicity when treated with gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes AA + AC.		[ 2]
Allele C	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Gemcitabine	N.A.	Neutropenia	Allele C is not associated with clearance of gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to allele A.		[ 3]
Genotype AC	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Gemcitabine	N.A.	Neoplasms	Patients with the AC genotype and cancer may have increased survival time and an increased risk for hematologic toxicity when treated with gemcitabine as compared to patients with the CC genotype. Other genetic and clinical factors may also influence toxicity and response in patients receiving gemcitabine.		[ 2]
Genetic Polymorphism	rs11854484
Site of GPD	chr15:45253280 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	C>T
Minor Allele Frequency	T=0.3029/1517 (Global)
Genotype CC	Click to Show/Hide the Full List of Affected Drugs:           8 Drugs in Total
Gemcitabine	Drug Info	Non-Small-Cell Lung Carcinoma	Correlated with the decreased drug response in patients (compare with Genotypes CT + TT); Correlated with the decreased hematologic toxicity risk in patients (compare with Genotypes CT + TT)		[ 2]
Gemcitabine	N.A.	Neutropenia	Genotype CC is associated with decreased risk of hematologic toxicity when treated with gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes CT + TT.		[ 2]
Gemcitabine	N.A.	Non-small Cell Lung Carcinoma	Genotype CC is associated with decreased response to gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes CT + TT.		[ 2]
Peginterferon Alfa-2b	N.A.	Hepatitis C Virus Infection	Patients with the CC genotype and hepatitis C may have a decreased risk for anemia when treated with protease inhibitors plus ribavirin and peginterferon, as compared to patients with the TT genotype. Other genetic and clinical factors may also influence risk for anemia.		[ 5]
Protease Inhibitors	N.A.	Hepatitis C Virus Infection	Patients with the CC genotype and hepatitis C may have a decreased risk for anemia when treated with protease inhibitors plus ribavirin and peginterferon, as compared to patients with the TT genotype. Other genetic and clinical factors may also influence risk for anemia.		[ 5]
Ribavirin	N.A.	Hepatitis C Virus Infection	Patients with the CC genotype and hepatitis C may have a decreased risk for anemia when treated with protease inhibitors plus ribavirin and peginterferon, as compared to patients with the TT genotype. Other genetic and clinical factors may also influence risk for anemia.		[ 5]
Tenofovir Disoproxil Fumarate	N.A.	HIV Infectious Disease	Patients with HIV and the CC genotype may experience a decreased severity of nephrotoxicity when treated with tenofovir disoproxil fumarate as compared to patients with the CT or TT genotypes. Other genetic and clinical factors may also affect severity of nephrotoxicity.		[ 6]
Tenofovir Disoproxil Fumarate	N.A.	Nephrotoxicity	Patients with HIV and the CC genotype may experience a decreased severity of nephrotoxicity when treated with tenofovir disoproxil fumarate as compared to patients with the CT or TT genotypes. Other genetic and clinical factors may also affect severity of nephrotoxicity.		[ 6]
Genotype TT	Click to Show/Hide the Full List of Affected Drugs:         12 Drugs in Total
Ribavirin	Drug Info	Hepatitis C	Correlated with the increased anemia risk in patients (compare with genotypes CC + CT)		[ 4]
Peginterferon alfa-2B	Drug Info	Hepatitis C	Correlated with the increased anemia risk in patients (compare with genotypes CC + CT)		[ 4]
Peginterferon Alfa-2b	N.A.	Anemia	Genotype TT is associated with increased risk of Anemia when treated with peginterferon alfa-2b, protease inhibitors and ribavirin in people with Hepatitis C as compared to genotypes CC + CT.		[ 4]
Protease Inhibitors	N.A.	Anemia	Genotype TT is associated with increased risk of Anemia when treated with peginterferon alfa-2b, protease inhibitors and ribavirin in people with Hepatitis C as compared to genotypes CC + CT.		[ 4]
Ribavirin	N.A.	Anemia	Genotype TT is associated with increased risk of Anemia when treated with peginterferon alfa-2b, protease inhibitors and ribavirin in people with Hepatitis C as compared to genotypes CC + CT.		[ 4]
Gemcitabine	N.A.	Non-small Cell Lung Carcinoma	Patients with the TT genotype and non-small-cell lung cancer may have a longer median survival time when treated with gemcitabine as compared to patients with the CC genotype. Other genetic and clinical factors may also influence survival.		[ 2]
Peginterferon Alfa-2b	N.A.	Hepatitis C Virus Infection	Genotype TT is associated with increased risk of Anemia when treated with peginterferon alfa-2b, protease inhibitors and ribavirin in people with Hepatitis C as compared to genotypes CC + CT.		[ 4]
Protease Inhibitors	N.A.	Hepatitis C Virus Infection	Genotype TT is associated with increased risk of Anemia when treated with peginterferon alfa-2b, protease inhibitors and ribavirin in people with Hepatitis C as compared to genotypes CC + CT.		[ 4]
Ribavirin	N.A.	Hepatitis C Virus Infection	Genotype TT is associated with increased risk of Anemia when treated with peginterferon alfa-2b, protease inhibitors and ribavirin in people with Hepatitis C as compared to genotypes CC + CT.		[ 4]
Tenofovir Disoproxil Fumarate	N.A.	HIV Infectious Disease	Patients with HIV and the TT genotype may experience an increased severity of nephrotoxicity when treated with tenofovir disoproxil fumarate as compared to patients with the CC genotype. Other genetic and clinical factors may also affect severity of nephrotoxicity.		[ 5]
Tenofovir Disoproxil Fumarate	N.A.	Nephrotoxicity	Patients with HIV and the TT genotype may experience an increased severity of nephrotoxicity when treated with tenofovir disoproxil fumarate as compared to patients with the CC genotype. Other genetic and clinical factors may also affect severity of nephrotoxicity.		[ 5]
Protease Inhibitors	N.A.	Hepatitis C	Correlated with the increased anemia risk in patients (compare with genotypes CC + CT)		[ 4]
Allele T	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Tenofovir	N.A.	Mucositis	Allele T is not associated with clearance of tenofovir in people with HIV Infections as compared to allele C.		[ 6]
Genotypes CT + TT	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Tenofovir Disoproxil Fumarate	N.A.	Nephrotoxicity	Genotypes CT + TT are associated with increased severity of nephrotoxicity due to tenofovir disoproxil fumarate in people with HIV Infections as compared to genotype CC.		[ 5]
Tenofovir Disoproxil Fumarate	N.A.	HIV Infectious Disease	Genotypes CT + TT are associated with increased severity of nephrotoxicity due to tenofovir disoproxil fumarate in people with HIV Infections as compared to genotype CC.		[ 5]
Genotype CT	Click to Show/Hide the Full List of Affected Drugs:           6 Drugs in Total
Gemcitabine	N.A.	Non-small Cell Lung Carcinoma	Patients with the CT genotype and non-small-cell lung cancer may have a longer median survival time when treated with gemcitabine as compared to patients with the CC genotype. Other genetic and clinical factors may also influence survival.		[ 2]
Peginterferon Alfa-2b	N.A.	Hepatitis C Virus Infection	Patients with the CT genotype and hepatitis C may have a decreased risk for anemia when treated with protease inhibitors plus ribavirin and peginterferon, as compared to patients with the TT genotype. Other genetic and clinical factors may also influence risk for anemia.		[ 4]
Protease Inhibitors	N.A.	Hepatitis C Virus Infection	Patients with the CT genotype and hepatitis C may have a decreased risk for anemia when treated with protease inhibitors plus ribavirin and peginterferon, as compared to patients with the TT genotype. Other genetic and clinical factors may also influence risk for anemia.		[ 4]
Ribavirin	N.A.	Hepatitis C Virus Infection	Patients with the CT genotype and hepatitis C may have a decreased risk for anemia when treated with protease inhibitors plus ribavirin and peginterferon, as compared to patients with the TT genotype. Other genetic and clinical factors may also influence risk for anemia.		[ 4]
Tenofovir Disoproxil Fumarate	N.A.	HIV Infectious Disease	Patients with HIV and the CT genotype may experience an increased severity of nephrotoxicity when treated with tenofovir disoproxil fumarate as compared to patients with the CC genotype. Other genetic and clinical factors may also affect severity of nephrotoxicity.		[ 5]
Tenofovir Disoproxil Fumarate	N.A.	Nephrotoxicity	Patients with HIV and the CT genotype may experience an increased severity of nephrotoxicity when treated with tenofovir disoproxil fumarate as compared to patients with the CC genotype. Other genetic and clinical factors may also affect severity of nephrotoxicity.		[ 5]
Genetic Polymorphism	rs2413775
Site of GPD	chr15:45252090 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	T>A
Minor Allele Frequency	T=0.5070/1003 (Global)
Genotype AA	Click to Show/Hide the Full List of Affected Drugs:           3 Drugs in Total
Valganciclovir	N.A.	Neutropenia	Genotype AA is not associated with increased risk of Neutropenia when treated with valganciclovir in people with Kidney Transplantation as compared to genotype TT.		[ 7]
Mercaptopurine	N.A.	Leukopenia	Genotype AA is associated with increased risk of Leukopenia when treated with mercaptopurine and methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype TT.		[ 8]
Methotrexate	N.A.	Leukopenia	Genotype AA is associated with increased risk of Leukopenia when treated with mercaptopurine and methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype TT.		[ 8]
Genotype AT	Click to Show/Hide the Full List of Affected Drugs:           3 Drugs in Total
Valganciclovir	N.A.	Neutropenia	Genotype AT is not associated with increased risk of Neutropenia when treated with valganciclovir in people with Kidney Transplantation as compared to genotype TT.		[ 7]
Mercaptopurine	N.A.	Neutropenia	Genotype AT is associated with increased risk of Neutropenia when treated with mercaptopurine and methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype TT.		[ 8]
Methotrexate	N.A.	Neutropenia	Genotype AT is associated with increased risk of Neutropenia when treated with mercaptopurine and methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype TT.		[ 8]
Allele A	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Methotrexate	N.A.	Mucositis	Allele A is not associated with risk of mucositis when treated with methotrexate in children with Lymphoma, Osteosarcoma or Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele T.		[ 9]
References
1	Gemcitabine metabolic and transporter gene polymorphisms are associated with drug toxicity and efficacy in patients with locally advanced pancreatic cancer. Cancer. 2010 Nov 15;116(22):5325-35.
2	Distribution of gemcitabine pathway genotypes in ethnic Asians and their association with outcome in non-small cell lung cancer patients. Lung Cancer. 2009 Jan;63(1):121-7.
3	Gene polymorphisms, pharmacokinetics, and hematological toxicity in advanced non-small-cell lung cancer patients receiving cisplatin/gemcitabine. Cancer Chemother Pharmacol. 2012 Jan;69(1):25-33.
4	Role of ITPA and SLC28A2 genes in the prediction of anaemia associated with protease inhibitor plus ribavirin and peginterferon in hepatitis C treatment. J Clin Virol. 2015 Jul;68:56-60.
5	Pharmacogenetic determinants of kidney-associated urinary and serum abnormalities in antiretroviral-treated HIV-positive patients. Pharmacogenomics J. 2020 Apr;20(2):202-212.
6	Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV. Pharmacogenet Genomics. 2023 Jun 01;33(4):79-87.
7	Multidrug resistance-associated protein 4 (MRP4) controls ganciclovir intracellular accumulation and contributes to ganciclovir-induced neutropenia in renal transplant patients. Pharmacol Res. 2016 Sep;111:501-508.
8	Genetic variants in 6-mercaptopurine pathway as potential factors of hematological toxicity in acute lymphoblastic leukemia patients. Pharmacogenomics. 2015;16(10):1119-34.
9	Association of MTHFR and ABCB1 polymorphisms with MTX-induced mucositis in Chinese paediatric patients with acute lymphoblastic leukaemia, lymphoma or osteosarcoma-A retrospective cohort study. J Clin Pharm Ther. 2021 Dec;46(6):1557-1563.

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