General Information of Drug Transporter (DT)
DT ID	DTD0028 Transporter Info
Gene Name	SLC47A2
Protein Name	Multidrug and toxin extrusion protein 2
Gene ID	146802
UniProt ID	Q86VL8
Genetic Polymorphisms of DT (GPD)
Genetic Polymorphism	rs12943590
Site of GPD	chr17:19716685 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	G>A
Minor Allele Frequency	A=0.3155/1580 (Global)
Allele A	Click to Show/Hide the Full List of Affected Drugs:           8 Drugs in Total
Metformin	Drug Info	Polycystic Ovary Syndrome	Irrelevant to the drug response in patients (compare with Allele G)		[ 1]
Metformin	Drug Info	Healthy Individuals	Irrelevant to the steady-state concentration of metformin in healthy individuals (compare with Allele G)		[ 2]
Metformin	N.A.	Leukemia, Myeloid, Acute	Allele A is not associated with exposure to metformin as compared to allele G.		[ 3]
Metformin	N.A.	Leukemia, Myeloid, Acute	Allele A is not associated with steady-state concentration of metformin in healthy individuals as compared to allele G.		[ 2]
Metformin	N.A.	Leukemia, Myeloid, Acute	Allele A is not associated with response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele G.		[ 4]
Metformin	N.A.	Leukemia, Myeloid, Acute	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	Allele A is associated with increased promoter activity in reporter assays and reduced binding to transcription repressor MZF-1 as compared to allele G.		[ 5]
Metformin	N.A.	Diabetes Mellitus	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:           8 Drugs in Total
Metformin	Drug Info	Healthy Individuals	Correlated with the decreased drug response in healthy individuals (compare with genotypes AG + GG); Correlated with the increased drug renal clearance and secretion clearance in healthy individuals (compare with genotype GG); Irrelevant to the differences in the plasma metformin concentration versus time curve or the maximum metformin concentration in healthy individuals (compare with genotype GG); Irrelevant to the drug glucose-lowering effect in healthy individuals (compare with genotype GG)		[ 6], [ 7]
Metformin	Drug Info	Diabetes Mellitus	Correlated with the decreased drug response in patients (compare with genotypes AG + GG)		[ 5]
Metformin	N.A.	Leukemia, Myeloid, Acute	Genotype AA is not associated with differences in the plasma metformin concentration versus time curve or the maximum metformin concentration when exposed to metformin in healthy individuals as compared to genotype GG.		[ 7]
Metformin	N.A.	Leukemia, Myeloid, Acute	Genotype AA is associated with decreased response to metformin in people with Diabetes Mellitus as compared to genotypes AG + GG.		[ 5]
Metformin	N.A.	Leukemia, Myeloid, Acute	Genotype AA is associated with decreased response to metformin when exposed to metformin in healthy individuals as compared to genotypes AG + GG.		[ 6]
Metformin	N.A.	Diabetes Mellitus	Genotype AA is associated with decreased response to metformin when exposed to metformin in healthy individuals as compared to genotypes AG + GG.		[ 6]
Metformin	N.A.	Diabetes Mellitus	Genotype AA is not associated with glucose-lowering effect of metformin when exposed to metformin in healthy individuals as compared to genotype GG.		[ 7]
Metformin	N.A.	Diabetes Mellitus	Genotype AA is associated with decreased response to metformin in people with Diabetes Mellitus as compared to genotypes AG + GG.		[ 5]
Genotype GG	Click to Show/Hide the Full List of Affected Drugs:           4 Drugs in Total
Metformin	Drug Info	Healthy Individuals	Irrelevant to the increased drug clearance in healthy individuals (compare with genotypes AA + AG)		[ 8]
Metformin	N.A.	Leukemia, Myeloid, Acute	Genotype GG is not associated with increased clearance of metformin in healthy individuals as compared to genotypes AA + AG.		[ 8]
Metformin	N.A.	Diabetes Mellitus	Patients with the GG genotype may have increased response to metformin in people with Diabetes Mellitus as compared to patients with the AA genotype. Other genetic and clinical factors may also influence a patient's response to metformin.		[ 6]
Metformin	N.A.	Diabetes Mellitus	Individuals with the GG genotype may have decreased renal and secretory clearance of metformin as compared to individuals with the AA genotype, however there are contradictory studies. Other genetic and clinical factors may also influence a patient's response to metformin.		[ 6]
Genotypes AA + AG	Click to Show/Hide the Full List of Affected Drugs:           3 Drugs in Total
Metformin	Drug Info	Healthy Individuals	Correlated with the increased renal and secretory drug clearance in healthy individuals (compare with genotype GG)		[ 6]
Metformin	N.A.	Leukemia, Myeloid, Acute	Genotypes AA + AG are associated with increased renal and secretory clearance of metformin when exposed to metformin in healthy individuals as compared to genotype GG.		[ 6]
Metformin	N.A.	Leukemia, Myeloid, Acute	Genotypes AA + AG is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to genotype GG.		[ 10]
Genotype AG	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Metformin	N.A.	Diabetes Mellitus	Patients with the AG genotype may have increased response to metformin in people with Diabetes Mellitus as compared to patients with the AA genotype. Other genetic and clinical factors may also influence a patient's response to metformin.		[ 6]
Metformin	N.A.	Diabetes Mellitus	Individuals with the AG genotype may have increased renal and secretory clearance of metformin as compared to individuals with the GG genotype, however there are contradictory studies. Other genetic and clinical factors may also influence a patient's response to metformin.		[ 6]
Genetic Polymorphism	rs34834489
Site of GPD	chr17:19716951 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	G>A
Minor Allele Frequency	A=0.2694/1349 (Global)
Genotype AA	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Metformin	Drug Info	Healthy Individuals	Correlated with the increased drug renal clearance and secretion clearance in healthy individuals (compare with genotype GG); Irrelevant to the differences in the plasma metformin concentration versus time curve or the maximum drug concentration in healthy individuals (compare with genotype GG); Irrelevant to the drug glucose-lowering effect in healthy individuals (compare with genotype GG)		[ 7]
Metformin	N.A.	Leukemia, Myeloid, Acute	Genotype AA is associated with increased renal clearance and secretion clearance of metformin when exposed to metformin in healthy individuals as compared to genotype GG.		[ 7]
Genotype AG	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Metformin	N.A.	Diabetes Mellitus	Patients with the AG genotype who are treated with metformin may have increased renal clearance and secretion clearance of metformin as compared to patients with the GG genotype or may have decreased renal clearance and secretion clearance of metformin but no differences in the plasma metformin concentration and no association with glucose-lowering effect as compared to patients with the AA genotype. Other genetic and clinical factors may also influence a patient's response to metformin.		[ 7]
Genotype GG	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Metformin	N.A.	Diabetes Mellitus	Patients with the GG genotype who are treated with metformin may have decreased renal clearance and secretion clearance of metformin but no differences in the plasma metformin concentration and no association with glucose-lowering effect as compared to patients with the AA genotype. Other genetic and clinical factors may also influence a patient's response to metformin.		[ 7]
Genetic Polymorphism	rs4621031
Site of GPD	chr17:19646957 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	T>A / T>C / T>G
Minor Allele Frequency	T=0.6740/1333 (Global)
Allele C	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Metformin	N.A.	Leukemia, Myeloid, Acute	Allele C is associated with decreased response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele T.		[ 10]
Genetic Polymorphism	rs34399035
Site of GPD	chr17:19681658 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	C>A / C>T
Minor Allele Frequency	C=0.9950/1969 (Global)
Allele T	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Metformin	N.A.	Leukemia, Myeloid, Acute	Allele T is associated with decreased metformin uptake in HEK-293 cells and reduction in protein expression levels when exposed to metformin as compared to allele C.		[ 5]
Metformin	N.A.	Leukemia, Myeloid, Acute	Allele T is not associated with decreased clinical benefit to metformin in people with Diabetes Mellitus, Type 2 as compared to allele C.		[ 12]
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	Steady-state pharmacokinetics of metformin is independent of the OCT1 genotype in healthy volunteers. Eur J Clin Pharmacol. 2015 Jun;71(6):691-697.
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	Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis. Clin Pharmacol Ther. 2017 Jun;101(6):763-772.
5	A common 5'-UTR variant in MATE2-K is associated with poor response to metformin. Clin Pharmacol Ther. 2011 Nov;90(5):674-84.
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	Functional characterization of MATE2-K genetic variants and their effects on metformin pharmacokinetics. Pharmacogenet Genomics. 2013 Jul;23(7):365-73.
8	Influences of organic cation transporter polymorphisms on the population pharmacokinetics of metformin in healthy subjects. AAPS J. 2013 Apr;15(2):571-80.
9	Implication of critical pharmacokinetic gene variants on therapeutic response to metformin in Type 2 diabetes. Pharmacogenomics. 2018 Jul 01;19(11):905-911.
10	Using EHR-Linked Biobank Data to Study Metformin Pharmacogenomics. Stud Health Technol Inform. 2015;210:914-8.
11	Effects of genetic variants of organic cation transporters on metformin response in newly diagnosed patients with type 2 diabetes. Medicine (Baltimore). 2024 Nov 29;103(48):e40684.

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