General Information of Drug Transporter (DT)
DT ID	DTD0007 Transporter Info
Gene Name	SLC47A1
Protein Name	Multidrug and toxin extrusion protein 1
Gene ID	55244
UniProt ID	Q96FL8
Genetic Polymorphisms of DT (GPD)
Genetic Polymorphism	rs2252281
Site of GPD	chr17:19533874 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	T>C
Minor Allele Frequency	C=0.3035/1520 (Global)
Allele C	Click to Show/Hide the Full List of Affected Drugs:         10 Drugs in Total
Metformin	Drug Info	Polycystic Ovary Syndrome	Irrelevant to the drug response in patients (compare with Allele T)		[ 1]
Metformin	N.A.	Neoplasms	Allele C is not associated with CLrenal nor the secretory clearance (CLsec) of metformin when exposed to metformin in healthy individuals as compared to allele T.		[ 2]
Metformin	N.A.	Neoplasms	Allele C is not associated with exposure to metformin as compared to allele T.		[ 3]
Metformin	N.A.	Neoplasms	Allele C is not associated with steady-state concentration of metformin in healthy individuals as compared to allele T.		[ 4]
Metformin	N.A.	Neoplasms	Allele C is not associated with response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele T.		[ 5]
Metformin	N.A.	Drug Toxicity	Allele C is not associated with response to metformin in women with Polycystic Ovary Syndrome as compared to allele T.		[ 1]
Metformin	N.A.	Diabetes Mellitus, Type 2	Allele C is not associated with CLrenal nor the secretory clearance (CLsec) of metformin when exposed to metformin in healthy individuals as compared to allele T.		[ 2]
Metformin	N.A.	Polycystic Ovary Syndrome	Allele C is not associated with CLrenal nor the secretory clearance (CLsec) of metformin when exposed to metformin in healthy individuals as compared to allele T.		[ 2]
Metformin	N.A.	Diabetes Mellitus, Type 2	Allele C is not associated with response to metformin in women with Polycystic Ovary Syndrome as compared to allele T.		[ 1]
Metformin	N.A.	Polycystic Ovary Syndrome	Allele C is not associated with response to metformin in women with Polycystic Ovary Syndrome as compared to allele T.		[ 1]
Genotype CC	Click to Show/Hide the Full List of Affected Drugs:           5 Drugs in Total
Metformin	Drug Info	Healthy Individuals	Correlated with the increased drug response in healthy individuals (compare with Genotypes CT + TT)		[ 6]
Metformin	Drug Info	Diabetes Mellitus	Correlated with the increased drug response in patients (compare with Genotypes CT + TT)		[ 6]
Metformin	N.A.	Neoplasms	Genotype CC is associated with increased response to metformin when treated with metformin in people with Diabetes Mellitus, Type 2 as compared to genotypes CT + TT.		[ 6]
Metformin	N.A.	Diabetes Mellitus, Type 2	Genotype CC is associated with increased response to metformin when exposed to metformin in healthy individuals as compared to genotypes CT + TT.		[ 6]
Metformin	N.A.	Polycystic Ovary Syndrome	Genotype CC is associated with increased response to metformin when exposed to metformin in healthy individuals as compared to genotypes CT + TT.		[ 6]
Genotype CT	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Metformin	N.A.	Diabetes Mellitus, Type 2	Patients with the CT genotype and Diabetes Mellitus, Type 2 who are treated with metformin may have a decreased response as compared to patients with the CC genotype, although this is contradicted in one study. Other genetic and clinical factors may also influence patient's response to metformin.		[ 6]
Metformin	N.A.	Polycystic Ovary Syndrome	Patients with the CT genotype and Diabetes Mellitus, Type 2 who are treated with metformin may have a decreased response as compared to patients with the CC genotype, although this is contradicted in one study. Other genetic and clinical factors may also influence patient's response to metformin.		[ 6]
Genotype TT	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Metformin	N.A.	Diabetes Mellitus, Type 2	Patients with the TT genotype and Diabetes Mellitus, Type 2 who are treated with metformin may have a decreased response as compared to patients with the CC genotype, although this is contradicted in one study. Other genetic and clinical factors may also influence patient's response to metformin.		[ 6]
Metformin	N.A.	Polycystic Ovary Syndrome	Patients with the TT genotype and Diabetes Mellitus, Type 2 who are treated with metformin may have a decreased response as compared to patients with the CC genotype, although this is contradicted in one study. Other genetic and clinical factors may also influence patient's response to metformin.		[ 6]
Genetic Polymorphism	rs2289669
Site of GPD	chr17:19560030 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	G>A
Minor Allele Frequency	A=0.3552/1779 (Global)
Allele A	Click to Show/Hide the Full List of Affected Drugs:         17 Drugs in Total
Metformin	Drug Info	Diabetes Mellitus	Irrelevant to the drug response in patients (compare with Allele G)		[ 5]
Metformin	Drug Info	Polycystic Ovary Syndrome	Irrelevant to the drug response in patients (compare with Allele G)		[ 1]
Tipiracil Hydrochloride	N.A.	Neoplasms	Allele A is not associated with response to tipiracil hydrochloride and trifluridine in people with Colorectal Neoplasms as compared to allele G.		[ 9]
Trifluridine	N.A.	Neoplasms	Allele A is not associated with response to tipiracil hydrochloride and trifluridine in people with Colorectal Neoplasms as compared to allele G.		[ 9]
Metformin	N.A.	Neoplasms	Allele A is not associated with CLrenal nor the secretory clearance (CLsec) of metformin when exposed to metformin in healthy individuals as compared to allele G.		[ 2]
Metformin	N.A.	Neoplasms	Allele A is not associated with exposure to metformin as compared to allele G.		[ 3]
Metformin	N.A.	Neoplasms	Allele A is associated with decreased response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele G.		[ 12]
Metformin	N.A.	Neoplasms	Allele A is not associated with steady-state concentration of metformin in healthy individuals as compared to allele G.		[ 4]
Metformin	N.A.	Neoplasms	Allele A is not associated with response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele G.		[ 5]
Platinum Compounds	N.A.	Drug Toxicity	Allele A is not associated with severity of Drug Toxicity when treated with Platinum compounds in people with Carcinoma, Non-Small-Cell Lung as compared to allele G.		[ 14]
Metformin	N.A.	Drug Toxicity	Allele A is associated with increased clinical benefit to metformin and sulfonamides, urea derivatives in people with Diabetes Mellitus, Type 2 as compared to allele G.		[ 15]
Sulfonamides, Urea Derivatives	N.A.	Drug Toxicity	Allele A is associated with increased clinical benefit to metformin and sulfonamides, urea derivatives in people with Diabetes Mellitus, Type 2 as compared to allele G.		[ 15]
Metformin	N.A.	Drug Toxicity	Allele A is not associated with response to metformin in women with Polycystic Ovary Syndrome as compared to allele G.		[ 1]
Metformin	N.A.	Diabetes Mellitus, Type 2	Allele A is not associated with response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele G.		[ 5]
Metformin	N.A.	Polycystic Ovary Syndrome	Allele A is not associated with response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele G.		[ 5]
Metformin	N.A.	Diabetes Mellitus, Type 2	Allele A is not associated with response to metformin in women with Polycystic Ovary Syndrome as compared to allele G.		[ 1]
Metformin	N.A.	Polycystic Ovary Syndrome	Allele A is not associated with response to metformin in women with Polycystic Ovary Syndrome as compared to allele G.		[ 1]
Genotype AA	Click to Show/Hide the Full List of Affected Drugs:           6 Drugs in Total
Metformin	Drug Info	Diabetes Mellitus	Correlated with the increased drug response in patients (compare with genotypes AG + GG)		[ 11], [ 12]
Metformin	N.A.	Neoplasms	Genotype AA is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to genotypes AG + GG.		[ 12]
Metformin	N.A.	Neoplasms	Genotype AA is associated with lack of increase in metformin concentrations when treated with metformin and trimethoprim in healthy individuals.		[ 13]
Trimethoprim	N.A.	Neoplasms	Genotype AA is associated with lack of increase in metformin concentrations when treated with metformin and trimethoprim in healthy individuals.		[ 13]
Metformin	N.A.	Diabetes Mellitus, Type 2	Genotype AA is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to genotypes AG + GG.		[ 12]
Metformin	N.A.	Polycystic Ovary Syndrome	Genotype AA is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to genotypes AG + GG.		[ 12]
Genotype GG	Click to Show/Hide the Full List of Affected Drugs:           6 Drugs in Total
Metformin	Drug Info	Diabetes Mellitus	Correlated with the increased drug response in patients (compare with genotypes AA + AG)		[ 14]
Metformin	N.A.	Drug Toxicity	Genotype GG is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to genotypes AA + AG.		[ 14]
Metformin	N.A.	Diabetes Mellitus, Type 2	Genotype GG is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to genotypes AA + AG.		[ 14]
Metformin	N.A.	Polycystic Ovary Syndrome	Genotype GG is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to genotypes AA + AG.		[ 14]
Metformin	N.A.	Diabetes Mellitus, Type 2	Patients with genotype GG may have decreased response to metformin in people with diabetes mellitus or polycystic ovarian syndrome as compared to patients with genotype AA, though other evidence contradicts this association depending on the measure of response. Other genetic and clinical factors may also influence the response to metformin.		[ 12]
Metformin	N.A.	Polycystic Ovary Syndrome	Patients with genotype GG may have decreased response to metformin in people with diabetes mellitus or polycystic ovarian syndrome as compared to patients with genotype AA, though other evidence contradicts this association depending on the measure of response. Other genetic and clinical factors may also influence the response to metformin.		[ 12]
Genotype AG	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Metformin	N.A.	Diabetes Mellitus, Type 2	Patients with genotype AG may have decreased response to metformin in people with diabetes mellitus or polycystic ovarian syndrome as compared to patients with genotype AA, though other evidence contradicts this association depending on the measure of response. Other genetic and clinical factors may also influence the response to metformin.		[ 12]
Metformin	N.A.	Polycystic Ovary Syndrome	Patients with genotype AG may have decreased response to metformin in people with diabetes mellitus or polycystic ovarian syndrome as compared to patients with genotype AA, though other evidence contradicts this association depending on the measure of response. Other genetic and clinical factors may also influence the response to metformin.		[ 12]
Genetic Polymorphism	rs2120274
Site of GPD	chr17:19614455 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	A>G / A>T
Minor Allele Frequency	A=0.3510/694 (Global)
Allele A	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Metformin	N.A.	Neoplasms	Allele A is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele G.		[ 15]
Genetic Polymorphism	rs8065082
Site of GPD	chr17:19561878 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	C>T
Minor Allele Frequency	C=0.5350/1058 (Global)
Genotypes CT + TT	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Metformin	N.A.	Neoplasms	Genotypes CT + TT is associated with increased response to metformin in people with Glucose Intolerance as compared to genotype CC.		[ 16]
References
1	The Pharmacogenetics of Metformin in Women with Polycystic Ovary Syndrome: A Randomized Trial. Basic Clin Pharmacol Toxicol. 2018 Feb;122(2):239-244.
2	A gene-gene interaction between polymorphisms in the OCT2 and MATE1 genes influences the renal clearance of metformin. Pharmacogenet Genomics. 2013 Oct;23(10):526-34.
3	Influence of pharmacogenetic polymorphisms and demographic variables on metformin pharmacokinetics in an admixed Brazilian cohort. Br J Clin Pharmacol. 2018 May;84(5):987-996.
4	Steady-state pharmacokinetics of metformin is independent of the OCT1 genotype in healthy volunteers. Eur J Clin Pharmacol. 2015 Jun;71(6):691-697.
5	Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis. Clin Pharmacol Ther. 2017 Jun;101(6):763-772.
6	The effect of novel promoter variants in MATE1 and MATE2 on the pharmacokinetics and pharmacodynamics of metformin. Clin Pharmacol Ther. 2013 Feb;93(2):186-94.
7	Potential role of polymorphisms in the transporter genes ENT1 and MATE1/OCT2 in predicting TAS-102 efficacy and toxicity in patients with refractory metastatic colorectal cancer. Eur J Cancer. 2017 Nov;86:197-206.
8	A gene variant near ATM affects the response to metformin and metformin plasma levels: a post hoc analysis of an RCT. Pharmacogenomics. 2018 Jun 01;19(8):715-726.
9	Associations of genetic polymorphisms of the transporters organic cation transporter 2 (OCT2), multidrug and toxin extrusion 1 (MATE1), and ATP-binding cassette subfamily C member 2 (ABCC2) with platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients. Chin J Cancer. 2016 Sep 2;35(1):85.
10	Association of SLC22A1, SLC47A1, and KCNJ11 polymorphisms with efficacy and safety of metformin and sulfonylurea combination therapy in Egyptian patients with type 2 diabetes. Res Pharm Sci. 2023 Dec;18(6):614-625.
11	Pharmacogenomic association between a variant in SLC47A1 gene and therapeutic response to metformin in type 2 diabetes. Diabetes Obes Metab. 2013 Feb;15(2):189-91.
12	SLC47A1 gene rs2289669 G>A variants enhance the glucose-lowering effect of metformin via delaying its excretion in Chinese type 2 diabetes patients. Diabetes Res Clin Pract. 2015 Jul;109(1):57-63.
13	Trimethoprim-metformin interaction and its genetic modulation by OCT2 and MATE1 transporters. Br J Clin Pharmacol. 2013 Nov;76(5):787-96.
14	The Impacts of SLC22A1 rs594709 and SLC47A1 rs2289669 Polymorphisms on Metformin Therapeutic Efficacy in Chinese Type 2 Diabetes Patients.
15	Using EHR-Linked Biobank Data to Study Metformin Pharmacogenomics. Stud Health Technol Inform. 2015;210:914-8.
16	Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program. Diabetes. 2010 Oct;59(10):2672-81.

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