Table 3.
Genetic variants in human organic cation transporters of the SLC22A family.
| Transporter (Gene) | Genetic Polymorphism | Amino Acid Change | Effect on Expression | Activity | Effect on Drug Disposition |
|---|---|---|---|---|---|
| OCT1 (SLC22A1) | c.181C>T | R61C | = | Reduced | Reduced intestinal uptake of metformin |
| Higher plasma concentrations of O-desmethyltramadol, sumatriptan, morphine, tropisetron, ondansetron | |||||
| c.252T>C | C88R | = | Reduced | Increased systemic exposure to sumatriptan | |
| c.1201G>A | G401S | = | Reduced | Reduced intestinal uptake of metformin | |
| Higher plasma concentrations of O-desmethyltramadol, sumatriptan, morphine, tropisetron, ondansetron | |||||
| c.1222A>G | M408V | = | Similar | Gastrointestinal side-effects of metformin | |
| Alteration of lamotrigine serum concentration | |||||
| c.1258_1260delATG | M420del | = | Reduced | Reduced intestinal uptake of metformin | |
| Higher plasma concentrations of O-desmethyltramadol, morphine, tropisetron, ondansetron | |||||
| c.1386A>C (rs622342) | - | ↓Expected | Reduced | Low effect of metformin, levodopa | |
| c.1393G>C | G465R | = | Reduced | Reduced intestinal uptake of metformin | |
| Increased systemic exposure to sumatriptan | |||||
| OCT*5 | G465R + M420del | = | Reduced | Higher plasma concentrations of O-desmethyltramadol, morphine, tropisetron and ondansetron | |
| OCT1*6 | C88R + M420del | = | Reduced | Higher plasma concentrations of O-desmethyltramadol, morphine, tropisetron and ondansetron | |
| rs36056065 (c.1276 + 1ins GTAAGTTG) | - | Aberrant splicing | Gastrointestinal side-effects of metformin | ||
| OCT2 (SLC22A2) | c.495G>A | M165I | Reduced | ||
| c.596C>G | T199I | Reduced | Reduced renal clearance of metformin | ||
| c.602C>T | T201M | Reduced | Reduced renal clearance of metformin | ||
| c.808G>T | A270S | Reduced | Reduced renal clearance of metformin | ||
| c.1198C>T | R400C | Reduced | |||
| c.1294A>C | K432Q | Similar | |||
| OCT3 (SLC22A3) | A116S | = | Reduced | ||
| T400I | = | Reduced | |||
| A439V | = | Reduced | |||
| OCTN1 (SLC22A4) | c.188G>A | R63H | ↓Membrane | Reduced | |
| c.248G>C | R83P | ↓Membrane | Reduced | ||
| c.400C>A | L134M | Similar | |||
| c.475G>A | V159M | Similar | |||
| c.494A>G | D165G | ↓Membrane | Lost | ||
| c.615G>A | M205I | ↓Membrane | Reduced | ||
| c.774G>C | M258I | Similar | |||
| c.844C>T | K282X | Lost | |||
| c.917C>T | T306I | = | Similar | ||
| c.1031T>A | M344K | Similar | |||
| c.1445G>A | G482D | = | Reduced | ||
| c.1460T>C | M487T | Similar | |||
| c.1499T>A | I500N | = | Reduced | ||
| c.1507G>A | L503F | = | Reduced | Reduced tubular secretion of gabapentin | |
| c.1531G>A | = | Reduced | |||
| OCTN2 (SLC22A5) | c.51C>G | F17L | Reduced | ||
| c.325G>C | E109Q | Similar | |||
| c.364G>T | D122Y | ↓Membrane | Reduced | ||
| c.430C>T | L144F | Similar | |||
| c.523G>A | V175M | Similar | |||
| c.573G>T | K191N | Similar | |||
| c.614C>T | A214V | Similar | |||
| c.791C>T | T264M | Reduced | |||
| c.904A>G | K302E | ↓Membrane | Reduced | ||
| c.934A>G | I312V | Similar | |||
| c.949G>A | E317K | Higher | |||
| M352R | = | Lost | |||
| c.1345T>G | Y449D | Reduced | |||
| P478L | = | Lost | |||
| c.1341TG>T | V481F | Reduced | |||
| V481I | Similar | ||||
| c.1463G>A | R488H | Similar | |||
| c.1522T>C | F508L | Similar | |||
| c.1588A>G | M530V | Similar | |||
| c.1645C>T | P549S | Similar |