TABLE 12

In vitro characterization of genetic polymorphisms in OATP1A2, -1B1, and -1B3

In vitro function was assessed using prototypical substrates for OATP1A2 (estrone-3-sulfate), OATP1B1 (estrone-3-sulfate, estradiol 17β-glucuronide, rifampin), and OATP1B3 (estrone-3-sulfate, estradiol 17β-glucuronide). Some nucleotide positions were confirmed by PharmGKB (Hewett et al., 2002). OATP1A2 data from Lee et al. (2005a) and Badagnani et al. (2006). OATP1B1 data from Tirona et al. (2001); Michalski et al. (2002); Nozawa et al. (2002); Nishizato et al. (2003); Tirona et al. (2003); Iwai et al. (2004a); Morimoto et al. (2004); Kameyama et al. (2005). OATP1B3 data from Letschert et al. (2004).

Nucleotide ChangeAmino Acid ChangeIn Vitro FunctionProtein Expression/Localization
SLCO1A2OATP1A2
    T38C    I13T↑↔Normal
    A382T    N128Y↔N.D.
    A404T    N135I↓↔N.D.
    C502T    R168C↓N.D.
    A516C    E172D↓Intracellular
    G559A    A187T↓Normal
    A833-    Asn278STOP↓N.D.
    C2003G    T668S↔Intracellular
SLCO1B1OATP1B1
    T217C    F73L↓Intracellular
    T245C    V82A↓Intracellular
    A388G    N130D↓↔Normal
    A452G    N151SN.D.N.D.
    C463A    P155T↔Normal
    A467G    E156G↓Normal
    T521C    V174A↓Intracellular/normal
    T578G    L193R↓Intracellular
    C1007G    P336RN.D.N.D.
    T1058C    I353T↓Intracellular
    A1294G    N432D↓↔Normal
    A1385G    D462G↔Normal
    G1454T    C485FN.D.N.D.
    G1463C    G488A↓Intracellular
    T1628G    L543WN.D.N.D.
    A1964G    D655G↓↔Normal
    A2000G    E667G↓↔Normal
SLCO1B3OATP1B3
    T334G    S112A↑↔Normal
    G699A    M233I↔Normal
    G1564T    G522C↓↔Reduced
    G1748A    G583E↓↔Reduced

  • ↓, reduced function; ↑, increased function; ↔, no change in function; N.D. not determined.