A cost effective RFLP method to genotype Solute carrier organic anion 1B1 (SLCO1B1) c.1929A>C (p.Leu643Phe, rs34671512); a variant with potential effect on rosuvastatin pharmacokinetics
| dc.contributor.author | Soko, Nyarai D | |
| dc.contributor.author | Masimirembwa, Collen | |
| dc.contributor.author | Dandara, Collet | |
| dc.date.accessioned | 2018-07-11T09:36:22Z | |
| dc.date.available | 2018-07-11T09:36:22Z | |
| dc.date.issued | 2018-06-14 | |
| dc.date.updated | 2018-06-17T03:36:09Z | |
| dc.description.abstract | Objective: This study describes a restriction fragment polymorphism protocol for rapidly screening the polymorphism SLCO1B1 c.1929A>C in genomic DNA samples. The polymorphism SLCO1B1 c.1929A>C has been associated with increased activity resulting in increased hepatic uptake of drugs. Currently SLCO1B1 c.1929A>C is genotyped using direct sequencing techniques and 5′ nuclease based assays which can be cost prohibiting in resource limited settings. The aim of this study therefore was to design and validate a cost effective RFLP for genotyping the SLCO1B1 c.1929A>C polymorphism. This study was designed to investigate the effect of the polymorphism SLCO1B1 c.1929A>C on interindividual variability in rosuvastatin pharmacokinetics in healthy volunteers of African descent. Results We describe a restriction fragment length polymorphism method to genotype SLCO1B1 c.1929A>C polymorphism using the restriction enzyme Ase1. A student’s t test with Welch correction was used to establish association between the SLCO1B1 c.1929A>C variant and rosuvastatin exposure. The frequency of the SLCO1B1 c.1929C allele amongst Zimbabweans was 6%. The SLCO1B1 c.1929C allele was associated with a 75% reduction (P < 0.001) in rosuvastatin exposure when compared to individuals carrying the wild type SLCO1B1 c.1929A allele. Polymorphism c.1929A>C may therefore play a significant role in rosuvastatin response. The RFLP method is quick and cost effective. | |
| dc.identifier.apacitation | Soko, N. D., Masimirembwa, C., & Dandara, C. (2018). A cost effective RFLP method to genotype Solute carrier organic anion 1B1 (SLCO1B1) c.1929A>C (p.Leu643Phe, rs34671512); a variant with potential effect on rosuvastatin pharmacokinetics. http://hdl.handle.net/11427/28290 | en_ZA |
| dc.identifier.chicagocitation | Soko, Nyarai D, Collen Masimirembwa, and Collet Dandara "A cost effective RFLP method to genotype Solute carrier organic anion 1B1 (SLCO1B1) c.1929A>C (p.Leu643Phe, rs34671512); a variant with potential effect on rosuvastatin pharmacokinetics." (2018) http://hdl.handle.net/11427/28290 | en_ZA |
| dc.identifier.citation | Soko, N. D., Masimirembwa, C., & Dandara, C. (2018). A cost effective RFLP method to genotype Solute carrier organic anion 1B1 (SLCO1B1) c. 1929A> C (p. Leu643Phe, rs34671512); a variant with potential effect on rosuvastatin pharmacokinetics. BMC research notes, 11(1), 384. | |
| dc.identifier.ris | TY - Journal Article AU - Soko, Nyarai D AU - Masimirembwa, Collen AU - Dandara, Collet AB - Objective: This study describes a restriction fragment polymorphism protocol for rapidly screening the polymorphism SLCO1B1 c.1929A>C in genomic DNA samples. The polymorphism SLCO1B1 c.1929A>C has been associated with increased activity resulting in increased hepatic uptake of drugs. Currently SLCO1B1 c.1929A>C is genotyped using direct sequencing techniques and 5′ nuclease based assays which can be cost prohibiting in resource limited settings. The aim of this study therefore was to design and validate a cost effective RFLP for genotyping the SLCO1B1 c.1929A>C polymorphism. This study was designed to investigate the effect of the polymorphism SLCO1B1 c.1929A>C on interindividual variability in rosuvastatin pharmacokinetics in healthy volunteers of African descent. Results We describe a restriction fragment length polymorphism method to genotype SLCO1B1 c.1929A>C polymorphism using the restriction enzyme Ase1. A student’s t test with Welch correction was used to establish association between the SLCO1B1 c.1929A>C variant and rosuvastatin exposure. The frequency of the SLCO1B1 c.1929C allele amongst Zimbabweans was 6%. The SLCO1B1 c.1929C allele was associated with a 75% reduction (P < 0.001) in rosuvastatin exposure when compared to individuals carrying the wild type SLCO1B1 c.1929A allele. Polymorphism c.1929A>C may therefore play a significant role in rosuvastatin response. The RFLP method is quick and cost effective. DA - 2018-06-14 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2018 T1 - A cost effective RFLP method to genotype Solute carrier organic anion 1B1 (SLCO1B1) c.1929A>C (p.Leu643Phe, rs34671512); a variant with potential effect on rosuvastatin pharmacokinetics TI - A cost effective RFLP method to genotype Solute carrier organic anion 1B1 (SLCO1B1) c.1929A>C (p.Leu643Phe, rs34671512); a variant with potential effect on rosuvastatin pharmacokinetics UR - http://hdl.handle.net/11427/28290 ER - | en_ZA |
| dc.identifier.uri | https://doi.org/10.1186/s13104-018-3469-4 | |
| dc.identifier.uri | http://hdl.handle.net/11427/28290 | |
| dc.identifier.vancouvercitation | Soko ND, Masimirembwa C, Dandara C. A cost effective RFLP method to genotype Solute carrier organic anion 1B1 (SLCO1B1) c.1929A>C (p.Leu643Phe, rs34671512); a variant with potential effect on rosuvastatin pharmacokinetics. 2018; http://hdl.handle.net/11427/28290. | en_ZA |
| dc.language.iso | en | |
| dc.publisher | BioMed Central | |
| dc.publisher.department | Division of Human Genetics | en_ZA |
| dc.publisher.faculty | Faculty of Health Sciences | en_ZA |
| dc.publisher.institution | University of Cape Town | |
| dc.rights.holder | The Author(s) | |
| dc.subject.other | SLCO1B1 | |
| dc.subject.other | Rosuvastatin | |
| dc.subject.other | African | |
| dc.subject.other | rs34671512 | |
| dc.subject.other | RFLP | |
| dc.subject.other | Pharmacogenetics | |
| dc.subject.other | Pharmacokinetics | |
| dc.subject.other | SLCO1B1*22 | |
| dc.subject.other | SLCO1B1*35 | |
| dc.title | A cost effective RFLP method to genotype Solute carrier organic anion 1B1 (SLCO1B1) c.1929A>C (p.Leu643Phe, rs34671512); a variant with potential effect on rosuvastatin pharmacokinetics | |
| dc.type | Journal Article | |
| uct.type.filetype | Text | |
| uct.type.filetype | Image |