Your browser doesn't support javascript.
loading
In vitro identification of decreased function phenotype ABCG2 variants.
Suominen, Laura; Sjöstedt, Noora; Vellonen, Kati-Sisko; Gynther, Mikko; Auriola, Seppo; Kidron, Heidi.
Afiliación
  • Suominen L; Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland.
  • Sjöstedt N; Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland.
  • Vellonen KS; School of Pharmacy, University of Eastern Finland, Kuopio FI-70210, Finland.
  • Gynther M; School of Pharmacy, University of Eastern Finland, Kuopio FI-70210, Finland.
  • Auriola S; School of Pharmacy, University of Eastern Finland, Kuopio FI-70210, Finland.
  • Kidron H; Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland. Electronic address: heidi.kidron@helsinki.fi.
Eur J Pharm Sci ; 188: 106527, 2023 Sep 01.
Article en En | MEDLINE | ID: mdl-37451410
Reduced activity of efflux transporter ABCG2, caused e.g., by inhibition or decreased function genetic variants, can increase drug absorption and plasma levels. ABCG2 has one clinically significant single nucleotide variant Q141K (c.421C>A), which leads to decreased protein levels and transport activity. In addition to Q141K, ABCG2 has over 500 rare (<1% minor allele frequency) nonsynonymous variants, but their functionality remains unknown. We studied the transport activity and abundance of 30 rare ABCG2 variants. The variants were transiently expressed in HEK293 cells. Transport activity and protein abundance were measured from inside-out crude membrane vesicles. Results were normalised to the reference ABCG2, while Q141K was used to categorise variants into decreased and normal function phenotypes based on their apparent transport activity. Fourteen variants (G80E, D128V, T434M, Q437R, C438R, C438W, C438Y, L479S, P480L, S486N, T512N, S519P, G553D and K647E) had similar or lower apparent transport activity than Q141K and thus were categorised as having a decreased function phenotype. Protein abundance could not explain all of the observed changes in transport activity: Only six variants (D128V, Q437R, C438R, S519P, G553D, and K647E) had similar or lower abundance compared to Q141K. The decreased function variants may increase systemic drug exposure and therefore cause interindividual variability in pharmacokinetics. In the future, in vitro phenotype classification may help to design personalised drug treatments.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo de Nucleótido Simple Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Revista: Eur J Pharm Sci Asunto de la revista: FARMACIA / FARMACOLOGIA / QUIMICA Año: 2023 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo de Nucleótido Simple Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Revista: Eur J Pharm Sci Asunto de la revista: FARMACIA / FARMACOLOGIA / QUIMICA Año: 2023 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Países Bajos