Transporters 1

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Author:
HUSOP2014
ID:
149413
Filename:
Transporters 1
Updated:
2012-04-30 18:34:28
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HUSOP Gen Final
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Description:
Transporters, gene, AA, location, effect, drugs
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  1. OATP1A2
    • Gene: SLCO1A2
    • Locations: Antiporter on Apical (intestine, brain, kidney, liver)
    • SNPs: T38C with I13T- Increase Methotrexate
    • SNPs: A516C with E172D- Decrease methotrexate, Deltorphin
    • SNPs: A833- with N278DEL- Decrease Methotrexate
    • Substrates: Fexofenadine, Methotrexate, deltorphin, ouabain, rosuvastatin, T4, T3, PGE2, EcG, E1S, TCA, DHEAS
  2. OATP1B1
    • Gene: SLCO1B1
    • Locations: Antiporter on Basolateral of liver)
    • SNPs: A388G with N130D- Decrease rifampin
    • SNPs: T521C with Vi74A- Decrease rifampin, statins
    • SNPs: T1058C with I353T- Decrease rifampin, rosuvastatin
    • Substrates: Benzylpenicillin, cerivastatin, atorvastatin, rosuvastatin, pitavastatin, capsofungin, rifampin, atrasentan, valsartan, olmesartan, enalapril, methotrexate
    • Clinical sign: OJ or GFJ (flavonoids) inhibit OATP1A2 decrease Fexofenadine
  3. OATP1B3
    • Gene: SLCO1B3
    • Location: antiporter on Basolateral of liver
    • SNP: T33G with S112A- Increase mycophenolic acid
    • SNP: G699A with M233I- Increase mycophenolic acid
    • SNP: G1564T with G522C- decrease E2G
    • Substrates: Pravastatin, fluvastatin, rifampicin, fexofenadine, digoxin, taurocholate, E2G, E1S, bilirubin, bilirubin-glucuronide
  4. RFC-1
    • Gene: SLC19A1
    • Location: Liver but every tissue broad distribution
    • SNP: G80A with R27H- increase Methotrexate
    • Substrates: methotrexate, raltitrexed, folate
    • Clinical sign: RA 3-4 fold remission in 80AA over 80GG
  5. OCT1
    • Gene: SLC22A1
    • Location: electrogenic uniporter on basolateral of Liver, heart, skeletal muscle, kidney, placenta, S. intestine
    • SNP: C41T with S14F -decrease Metformin, increase MPP
    • SNP: C181T with R61C- dec metformin
    • SNP: G1201A with G401S- dec metformin
    • SNP: G1393A with G465R- dec metformin
    • Substrates: Metformin, choline, acetylcholine, quinidine, imatinib, cimetidine, acyclovir, gancylovir
    • Clinical sign: imatinib better progression free/survival in CML
    • decreased metformin
  6. OCT2
    • Gene: SLC22A2
    • Location: electrogenic uniporter on Basolateral of Kidney, SI, thymus, Adrenal gland, neurons, choroid plexus, placenta
    • SNP: T481C with F161L- dec MPP
    • SNP: G808T with A270S- dec MPP, Metformin, Propranolol
    • SNP: C1198T with R400C- dec MPP
    • Substrates: metformin, choline, mepiperphenidol, cimetidine, famotidine, ranitidine, memantine, quinine, debrisoquine, cisplatin
    • Clinical Sign: G808T decreases renal cl of metformin
  7. OCTN2
    • Gene: SLC22A5
    • Location: proton antiporter on Kidney(apical), intestine(basolateral), lung
    • SNP: T1345G with T449D - dec L-carnitine
    • SNP: G1441A with V481I - dec L-carnitine
    • Substrates: Ipratropium, verapamil, quinidine, emetine, cephaloridine, choline, acetly-L-carnitine, carnitine
    • Clinical sign: risk toxicity due to reduced clearance
  8. T38C-I13T
    • Transporter: OATP1A2
    • Location: intestine (Apical), Kidey (basolateral)
    • Clinical sign: increased Methotrexate
    • Other: Naringin flavonoid (grapefruit juice) and Hsperidin flavonoid (orange juice) inhibit OATP1A2 and dec fexofenadine
  9. A516C with E172D
    • Transporter: OATP1A2
    • Location: intestine (Apical), Kidey (basolateral)
    • Clinical sign: decreased Methotrexate, Deltorpin II, E1S
    • Other: Naringin flavonoid (grapefruit juice) and Hsperidin flavonoid (orange juice) inhibit OATP1A2 and dec fexofenadine
  10. A833- with N278DEL
    • Transporter: OATP1A2
    • Location: intestine (Apical), Kidey (basolateral)
    • Clinical sign: decreased Methotrexate, E1S
    • Other: Naringin flavonoid (grapefruit juice) and Hsperidin flavonoid (orange juice) inhibit OATP1A2 and dec fexofenadine
  11. A388G with N130D
    • Transporter: OATP1B1
    • Location: Liver (basolateral)
    • Clinical sign: decrease Rifampin, no change rosu, prav, atorvastatins.
  12. T521C with V174A
    • Transporter: OATP1B1
    • Location: Liver (basolateral)
    • Clinical sign: decrease Rifampin, rosu, ceriva, atorvastatins. ezetimibe-glucuronide, E1S, E2G
    • Other: decreased expression and function of transporter
    • Drug: Rosuvastatin- 521CC-(CA)- increase AUC 217
    • and *1a/*5- (CA)- increase AUC 143
    • Drug: Pravastatin -*15/*15- (AS)- increase AUC 187
  13. T1058C with I353T
    • Transporter: OATP1B1
    • Location: Liver (basolateral)
    • Clinical sign: decrease Rifampin, rosuvastatin, E1S, E2G
  14. SNP: T33G with S112A
    • Transporter: OATP1B3
    • Location: Liver (basolateral)
    • Clincal sign: Increase mycophenolic acid
  15. SNP: G699A with M233I
    • Transporter: OATP1B3
    • Location: Liver (basolateral)
    • Clincal sign: Increase mycophenolic acid
  16. SNP: G1564T with G522C
    • Transporter: OATP1B3
    • Location: Liver (basolateral)
    • Clincal sign: decrease E2G
  17. SNP: G80A with R27H
    • Transporter: RFC-1
    • Location: Hepatic (basolateral), but every tissue
    • Clinical sign: increased methotrexate
    • Other: Remission of RA 3-4 fold higher in 80AA over 80GG, increased aminotransferase activity
  18. SNP: C41T with S14F
    • Transporter: OCT1
    • Location: Liver (basolateral), heart, skeletal muscle, kidney, placenta, SI
    • Clinical sign: decrease Metformin, increased MPP
    • Other: CML in higher OCT1 w/ imatinib, better response, progression free, survival over basline OCT1
    • Reduced function alleles: decreased response to metformin
  19. SNP: C181T with R61C
    • Transporter: OCT1
    • Location: Liver (basolateral), heart, skeletal muscle, kidney, placenta, SI
    • Clinical sign: decrease Metformin, MPP
    • Other: CML in higher OCT1 w/ imatinib, better response, progression free, survival over basline OCT1
    • Reduced function alleles: decreased response to metformin
  20. SNP: G1201A with G401S
    • Transporter: OCT1
    • Location: Liver (basolateral), heart, skeletal muscle, kidney, placenta, SI
    • Clinical sign: decrease Metformin, MPP
    • Other: CML in higher OCT1 w/ imatinib, better response, progression free, survival over basline OCT1
    • Reduced function alleles: decreased response to metformin
  21. SNP: G1393A with G465R
    • Transporter: OCT1
    • Location: Liver (basolateral), heart, skeletal muscle, kidney, placenta, SI
    • Clinical sign: decrease Metformin, MPP
    • Other: CML in higher OCT1 w/ imatinib, better response, progression free, survival over basline OCT1
    • Reduced function alleles: decreased response to metformin
  22. SNP: T481C with F161L
    • Transporter: OCT2 (electrogenic uniporter)
    • Location: Kidney (basolateral), SI, thymus, Adrenal gland, neurons, choroid plexus, placenta
    • Clinical sign: decreased MPP
  23. SNP: G808T with A270S
    • Transporter: OCT2 (electrogenic uniporter)
    • Location: Kidney (basolateral), SI, thymus, Adrenal gland, neurons, choroid plexus, placenta
    • Clinical sign: decreased MPP, Metformin, Propranolol
    • Other: 808TT decreases uptake, decreases renal cl
  24. SNP: C1198T with R400C
    • Transporter: OCT2 (electrogenic uniporter)
    • Location: Kidney (basolateral), SI, thymus, Adrenal gland, neurons, choroid plexus, placenta
    • Clinical sign: decreased MPP
  25. SNP: T1345G with T449D - dec L-carnitine
    • Transporter: OCTN2 (proton antiporter)
    • Location: Kidney (apical), intestine (basolateral), lung
    • Clinical sign: risk for toxicity due to reduced clearance
  26. SNP: G1441A with V481I - dec L-carnitine
    • Transporter: OCTN2 (proton antiporter)
    • Location: Kidney (apical), intestine (basolateral), lung
    • Clinical sign: risk for toxicity due to reduced clearance

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