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

• Published in: BMC research notes Vol. 11; no. 1; p. 384
• Main Authors: Soko, Nyarai D, Masimirembwa, Collen, Dandara, Collet
• Format: Journal Article
• Language: English
• Published: England BioMed Central 14-06-2018; BMC
• Subjects: African; Alleles; Consortia; Councils; Deoxyribonucleic acid; DNA; Enzymes; Ethics; Gene polymorphism; Genetic testing; Genetics; Genomes; Genotyping; Health sciences; Medical research; Methods; Nuclease; Pharmacogenetics; Pharmacokinetics; Research Note; Restriction fragment length polymorphism; RFLP; Rosuvastatin; rs34671512; SLCO1B1; South Africa; Zimbabwe; Iowa; United States > US; Massachusetts; Wisconsin; SLCO1B1; SLCO1B122; Pharmacogenetics; SLCO1B135; Rosuvastatin; Pharmacokinetics; RFLP; rs34671512; African
• ISSN: 1756-0500; 1756-0500
• DOI: 10.1186/s13104-018-3469-4

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.
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.