General Information of Drug Transporter (DT)
DT ID	DTD0024 Transporter Info
Gene Name	SLC22A6
Protein Name	Organic anion transporter 1
Gene ID	9356
UniProt ID	Q4U2R8
Genetic Polymorphisms of DT (GPD)
Genetic Polymorphism	rs11568626
Site of GPD	chr11:62984542 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	C>A / C>G / C>T
Minor Allele Frequency	T=0.0186/93 (Global)
Allele T	Click to Show/Hide the Full List of Affected Drugs:         20 Drugs in Total
Cidofovir	Drug Info	Cytomegalovirus Infection	Correlated with the decreased the drug K(m) (compare with Allele C); Irrelevant to the increased drug toxicity risk in patients (compare with allele C)		[ 1], [ 2]
Tenofovir	Drug Info	HIV Infection	Correlated with the decreased the drug K(m) (compare with Allele C); Irrelevant to the increased drug toxicity risk in patients (compare with allele C)		[ 1], [ 2]
Methotrexate	Drug Info	Acute B-Cell Leukemia	Irrelevant to the the drug uptake (compare wuth Allele C)		[ 3]
Adefovir Dipivoxil	Drug Info	Hepatitis B	Correlated with the decreased the drug K(m) (compare with Allele C); Irrelevant to the increased drug toxicity risk in patients (compare with allele C)		[ 1], [ 2]
Aminohippurate	N.A.	Hyperprolactinemia	Allele T is not associated with uptake of aminohippurate or methotrexate as compared to allele C.		[ 3]
Methotrexate	N.A.	Hyperprolactinemia	Allele T is not associated with uptake of aminohippurate or methotrexate as compared to allele C.		[ 3]
Adefovir Dipivoxil	N.A.	Hyperprolactinemia	Allele T is associated with decreased the K(m) for the nucleoside phosphonate analogs of adefovir dipivoxil, cidofovir or tenofovir as compared to allele C.		[ 2]
Cidofovir	N.A.	Hyperprolactinemia	Allele T is associated with decreased the K(m) for the nucleoside phosphonate analogs of adefovir dipivoxil, cidofovir or tenofovir as compared to allele C.		[ 2]
Tenofovir	N.A.	Hyperprolactinemia	Allele T is associated with decreased the K(m) for the nucleoside phosphonate analogs of adefovir dipivoxil, cidofovir or tenofovir as compared to allele C.		[ 2]
Atazanavir	N.A.	Drug Toxicity	Allele T is not associated with increased risk of Drug Toxicity when treated with atazanavir, lopinavir, ritonavir or tenofovir as compared to allele C.		[ 1]
Lopinavir	N.A.	Drug Toxicity	Allele T is not associated with increased risk of Drug Toxicity when treated with atazanavir, lopinavir, ritonavir or tenofovir as compared to allele C.		[ 1]
Ritonavir	N.A.	Drug Toxicity	Allele T is not associated with increased risk of Drug Toxicity when treated with atazanavir, lopinavir, ritonavir or tenofovir as compared to allele C.		[ 1]
Tenofovir	N.A.	Drug Toxicity	Allele T is not associated with increased risk of Drug Toxicity when treated with atazanavir, lopinavir, ritonavir or tenofovir as compared to allele C.		[ 1]
Adefovir Dipivoxil	N.A.	Drug Toxicity	Allele T is not associated with increased risk of Drug Toxicity when treated with atazanavir, lopinavir, ritonavir or tenofovir as compared to allele C.		[ 1]
Cidofovir	N.A.	Drug Toxicity	Allele T is not associated with increased risk of Drug Toxicity when treated with atazanavir, lopinavir, ritonavir or tenofovir as compared to allele C.		[ 1]
Tenofovir	N.A.	Drug Toxicity	Allele T is not associated with increased risk of Drug Toxicity when treated with atazanavir, lopinavir, ritonavir or tenofovir as compared to allele C.		[ 1]
Adefovir Dipivoxil	N.A.	Drug Toxicity	Allele T is not associated with uptake of aminohippurate or methotrexate as compared to allele C.		[ 3]
Cidofovir	N.A.	Drug Toxicity	Allele T is not associated with uptake of aminohippurate or methotrexate as compared to allele C.		[ 3]
Tenofovir	N.A.	Drug Toxicity	Allele T is not associated with uptake of aminohippurate or methotrexate as compared to allele C.		[ 3]
Aminohippurate	N.A.	Cancer	Irrelevant to the the drug uptake (compare wuth Allele C)		[ 3]
Genotype CC	Click to Show/Hide the Full List of Affected Drugs:           3 Drugs in Total
Adefovir Dipivoxil	N.A.	Drug Toxicity	CC genotype may be associated with a decreased affinity for the nucleoside phosphonate analogs cidofovir, adefovir, and tenofovir as compared with the TT or CT genotype. Other genetic and clinical factors may affect the transport of adefovir dipivoxil, cidofovir or tenofovir.		[ 2]
Cidofovir	N.A.	Drug Toxicity	CC genotype may be associated with a decreased affinity for the nucleoside phosphonate analogs cidofovir, adefovir, and tenofovir as compared with the TT or CT genotype. Other genetic and clinical factors may affect the transport of adefovir dipivoxil, cidofovir or tenofovir.		[ 2]
Tenofovir	N.A.	Drug Toxicity	CC genotype may be associated with a decreased affinity for the nucleoside phosphonate analogs cidofovir, adefovir, and tenofovir as compared with the TT or CT genotype. Other genetic and clinical factors may affect the transport of adefovir dipivoxil, cidofovir or tenofovir.		[ 2]
Genotype CT	Click to Show/Hide the Full List of Affected Drugs:           3 Drugs in Total
Adefovir Dipivoxil	N.A.	Drug Toxicity	CT genotype may be associated with an increased affinity for the nucleoside phosphonate analogs cidofovir, adefovir, and tenofovir as compared with the CC genotype. Other genetic and clinical factors may affect the transport of adefovir dipivoxil, cidofovir or tenofovir.		[ 2]
Cidofovir	N.A.	Drug Toxicity	CT genotype may be associated with an increased affinity for the nucleoside phosphonate analogs cidofovir, adefovir, and tenofovir as compared with the CC genotype. Other genetic and clinical factors may affect the transport of adefovir dipivoxil, cidofovir or tenofovir.		[ 2]
Tenofovir	N.A.	Drug Toxicity	CT genotype may be associated with an increased affinity for the nucleoside phosphonate analogs cidofovir, adefovir, and tenofovir as compared with the CC genotype. Other genetic and clinical factors may affect the transport of adefovir dipivoxil, cidofovir or tenofovir.		[ 2]
Genotype TT	Click to Show/Hide the Full List of Affected Drugs:           3 Drugs in Total
Adefovir Dipivoxil	N.A.	Drug Toxicity	TT genotype may be associated with an increased affinity for the nucleoside phosphonate analogs cidofovir, adefovir, and tenofovir as compared with the CC genotype. Other genetic and clinical factors may affect the transport of adefovir dipivoxil, cidofovir or tenofovir.		[ 2]
Cidofovir	N.A.	Drug Toxicity	TT genotype may be associated with an increased affinity for the nucleoside phosphonate analogs cidofovir, adefovir, and tenofovir as compared with the CC genotype. Other genetic and clinical factors may affect the transport of adefovir dipivoxil, cidofovir or tenofovir.		[ 2]
Tenofovir	N.A.	Drug Toxicity	TT genotype may be associated with an increased affinity for the nucleoside phosphonate analogs cidofovir, adefovir, and tenofovir as compared with the CC genotype. Other genetic and clinical factors may affect the transport of adefovir dipivoxil, cidofovir or tenofovir.		[ 2]
Genetic Polymorphism	rs11568634
Site of GPD	chr11:62979488 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	C>T
Allele T	Click to Show/Hide the Full List of Affected Drugs:           5 Drugs in Total
Adefovir Dipivoxil	Drug Info	HBV Infection	Correlated with the decreased drug uptake (compare with Allele C)		[ 3]
Adefovir Dipivoxil	Drug Info	Hepatitis B	Correlated with the decreased drug uptake (compare with Allele C); Irrelevant to the drug clearance in patients (compare with Allele C); Irrelevant to the nephrotoxicity risk in patients (compare with Allele C)		[ 3], [ 5]
Adefovir Dipivoxil	N.A.	Hyperprolactinemia	Allele T is associated with decreased uptake of adefovir dipivoxil as compared to allele C.		[ 3]
Adefovir Dipivoxil	N.A.	Nephrotoxicity	Allele T is not associated with increased risk of nephrotoxicity when treated with adefovir dipivoxil in people with Hepatitis B as compared to allele C.		[ 5]
Adefovir Dipivoxil	N.A.	Drug Toxicity	Allele T is not associated with increased risk of nephrotoxicity when treated with adefovir dipivoxil in people with Hepatitis B as compared to allele C.		[ 5]
Genotype CC	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Adefovir Dipivoxil	N.A.	Drug Toxicity	Genotype CC may be associated with increased uptake of adefovir dipivoxil as compared to genotype TT or CT. However, this has not been demonstrated clinically and other genetic and clinical factors may affect the renal clearance of adefovir.		[ 3]
Genotype CT	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Adefovir Dipivoxil	N.A.	Drug Toxicity	Genotype CT may be associated with decreased uptake of adefovir dipivoxil as compared to genotype CC. However, this has not been demonstrated clinically and other genetic and clinical factors may affect the renal clearance of adefovir.		[ 3]
Genotype TT	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Adefovir Dipivoxil	N.A.	Drug Toxicity	Genotype TT may be associated with decreased uptake of adefovir dipivoxil as compared to genotype CC. However, this has not been demonstrated clinically and other genetic and clinical factors may affect the renal clearance of adefovir.		[ 3]
Genetic Polymorphism	rs4149170
Site of GPD	chr11:62984817 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	C>T
Minor Allele Frequency	C=0.7900/1563 (Global)
Genotype TT	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Tenofovir	N.A.	Hyperprolactinemia	Genotype TT is associated with increased concentrations of tenofovir in people with Hepatitis B, Chronic as compared to genotypes CC + CT.		[ 5]
Allele C	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Raltegravir	N.A.	Hyperprolactinemia	Allele C is not associated with concentration of raltegravir in people with HIV Infections as compared to allele T.		[ 6]
Genotypes CT + TT	Click to Show/Hide the Full List of Affected Drugs:           4 Drugs in Total
Antineoplastic And Immunomodulating Agents	N.A.	Neutropenia	Genotypes CT + TT is associated with decreased severity of Neutropenia, Leukopenia, Thrombocytopenia or Anemia when treated with Antineoplastic And Immunomodulating Agents in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype CC.		[ 7]
Antineoplastic And Immunomodulating Agents	N.A.	Leukopenia	Genotypes CT + TT is associated with decreased severity of Neutropenia, Leukopenia, Thrombocytopenia or Anemia when treated with Antineoplastic And Immunomodulating Agents in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype CC.		[ 7]
Antineoplastic And Immunomodulating Agents	N.A.	Thrombocytopenia	Genotypes CT + TT is associated with decreased severity of Neutropenia, Leukopenia, Thrombocytopenia or Anemia when treated with Antineoplastic And Immunomodulating Agents in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype CC.		[ 7]
Antineoplastic And Immunomodulating Agents	N.A.	Anemia	Genotypes CT + TT is associated with decreased severity of Neutropenia, Leukopenia, Thrombocytopenia or Anemia when treated with Antineoplastic And Immunomodulating Agents in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype CC.		[ 7]
Allele T	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Tenofovir Disoproxil Fumarate	N.A.	Nephrotoxicity	Allele T is not associated with severity of nephrotoxicity due to tenofovir disoproxil fumarate in people with HIV Infections as compared to allele C.		[ 8]
Genetic Polymorphism	rs4149171
Site of GPD	chr11:62984710 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	T>A / T>C
Minor Allele Frequency	T=0.7670/1517 (Global)
Genotypes CC + CT	Click to Show/Hide the Full List of Affected Drugs:           4 Drugs in Total
Antineoplastic And Immunomodulating Agents	N.A.	Neutropenia	Genotypes CC + CT is associated with decreased severity of Neutropenia, Leukopenia, Thrombocytopenia or Anemia when treated with Antineoplastic And Immunomodulating Agents in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype TT.		[ 7]
Antineoplastic And Immunomodulating Agents	N.A.	Leukopenia	Genotypes CC + CT is associated with decreased severity of Neutropenia, Leukopenia, Thrombocytopenia or Anemia when treated with Antineoplastic And Immunomodulating Agents in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype TT.		[ 7]
Antineoplastic And Immunomodulating Agents	N.A.	Thrombocytopenia	Genotypes CC + CT is associated with decreased severity of Neutropenia, Leukopenia, Thrombocytopenia or Anemia when treated with Antineoplastic And Immunomodulating Agents in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype TT.		[ 7]
Antineoplastic And Immunomodulating Agents	N.A.	Anemia	Genotypes CC + CT is associated with decreased severity of Neutropenia, Leukopenia, Thrombocytopenia or Anemia when treated with Antineoplastic And Immunomodulating Agents in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype TT.		[ 7]
References
1	Polymorphisms associated with renal adverse effects of antiretroviral therapy in a Southern Brazilian HIV cohort. Pharmacogenet Genomics. 2015 Nov;25(11):541-7.
2	Functional consequences of single nucleotide polymorphisms in the human organic anion transporter hOAT1 (SLC22A6). J Pharmacol Exp Ther. 2005 Aug;314(2):923-31.
3	Functional analysis of polymorphisms in the organic anion transporter, SLC22A6 (OAT1). Pharmacogenet Genomics. 2005 Apr;15(4):201-9.
4	Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B. World J Gastroenterol. 2015 Feb 21;21(7):2116-23.
5	Pharmacogenetics of tenofovir drug transporters in the context of HBV: Is there an impact?. Biomed Pharmacother. 2024 Jun;175:116678.
6	High interpatient variability of raltegravir CSF concentrations in HIV-positive patients: a pharmacogenetic analysis. J Antimicrob Chemother. 2014 Jan;69(1):241-5.
7	Association between genetic variants of membrane transporters and the risk of high-grade hematologic adverse events in a cohort of Mexican children with B-cell acute lymphoblastic leukemia. Front Oncol. 2023;13:1276352.
8	Pharmacogenetic determinants of kidney-associated urinary and serum abnormalities in antiretroviral-treated HIV-positive patients. Pharmacogenomics J. 2020 Apr;20(2):202-212.

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