dc.contributor.author | Taskinen Suvi | |
dc.contributor.author | Viinamäki Jenni | |
dc.contributor.author | Tarkiainen E Katriina | |
dc.contributor.author | Tapaninen Tuija | |
dc.contributor.author | Tornio Aleksi | |
dc.contributor.author | Paile-Hyvarinen Maria | |
dc.contributor.author | Backman Janne T | |
dc.contributor.author | Neuvonen Mikko | |
dc.contributor.author | Niemi Mikko | |
dc.contributor.author | Lilius Tuomas O | |
dc.contributor.author | Lehtisalo Minna | |
dc.date.accessioned | 2022-10-27T12:23:49Z | |
dc.date.available | 2022-10-27T12:23:49Z | |
dc.identifier.uri | https://www.utupub.fi/handle/10024/158318 | |
dc.description.abstract | <h3>Aims</h3><p>The aim was to comprehensively investigate the effects of genetic variability on the pharmacokinetics of rosuvastatin.</p><h3>Methods</h3><p>We conducted a genome-wide association study and candidate gene analyses of single dose rosuvastatin pharmacokinetics in a prospective study (<em>n =</em> 159) and a cohort of previously published studies (<em>n =</em> 88).</p><h3>Results</h3><p>In a genome-wide association meta-analysis of the prospective study and the cohort of previously published studies, the <em>SLCO1B1</em> c.521 T > C (rs4149056) single nucleotide variation (SNV) associated with increased area under the plasma concentration–time curve (AUC) and peak plasma concentration of rosuvastatin (<em>P</em> = 1.8 × 10<sup>−12</sup> and <em>P</em> = 3.2 × 10<sup>−15</sup>). The candidate gene analysis suggested that the <em>ABCG2</em> c.421C > A (rs2231142) SNV associates with increased rosuvastatin AUC (<em>P</em> = .0079), while the <em>SLCO1B1</em> c.388A > G (rs2306283) and <em>SLCO2B1</em> c.1457C > T (rs2306168) SNVs associate with decreased rosuvastatin AUC (<em>P</em> = .0041 and <em>P</em> = .0076). Based on <em>SLCO1B1</em> genotypes, we stratified the participants into poor, decreased, normal, increased and highly increased organic anion transporting polypeptide (OATP) 1B1 function groups. The OATP1B1 poor function phenotype associated with 2.1-fold (90% confidence interval 1.6–2.8, <em>P =</em> 4.69 × 10<sup>−5</sup>) increased AUC of rosuvastatin, whereas the OATP1B1 highly increased function phenotype associated with a 44% (16–62%; <em>P</em> = .019) decreased rosuvastatin AUC. The <em>ABCG2</em> c.421A/A genotype associated with 2.2-fold (1.5–3.0; <em>P =</em> 2.6 × 10<sup>−4</sup>) increased AUC of rosuvastatin. The <em>SLCO2B1</em> c.1457C/T genotype associated with 28% decreased rosuvastatin AUC (11–42%; <em>P =</em> .01).</p><h3>Conclusion</h3><p>These data suggest roles for <em>SLCO1B1</em>, <em>ABCG2</em> and <em>SLCO2B1</em> in rosuvastatin pharmacokinetics. Poor <em>SLCO1B1</em> or <em>ABCG2</em> function genotypes may increase the risk of rosuvastatin-induced myotoxicity. Reduced doses of rosuvastatin are advisable for patients with these genotypes.</p> | |
dc.language.iso | en | |
dc.publisher | WILEY | |
dc.title | A comprehensive pharmacogenomic study indicates roles for SLCO1B1, ABCG2 and SLCO2B1 in rosuvastatin pharmacokinetics | |
dc.identifier.url | https://doi.org/10.1111/bcp.15485 | |
dc.identifier.urn | URN:NBN:fi-fe2022091258507 | |
dc.contributor.organization | fi=tyks, vsshp|en=tyks, vsshp| | |
dc.contributor.organization | fi=biolääketieteen laitos, yhteiset|en=Institute of Biomedicine| | |
dc.contributor.organization-code | 2607100 | |
dc.converis.publication-id | 176232622 | |
dc.converis.url | https://research.utu.fi/converis/portal/Publication/176232622 | |
dc.identifier.jour-issn | 0306-5251 | |
dc.okm.affiliatedauthor | Tornio, Aleksi | |
dc.okm.affiliatedauthor | Dataimport, tyks, vsshp | |
dc.okm.discipline | 3111 Biolääketieteet | fi_FI |
dc.okm.discipline | 3111 Biomedicine | en_GB |
dc.okm.internationalcopublication | not an international co-publication | |
dc.okm.internationality | International publication | |
dc.okm.type | Journal article | |
dc.publisher.country | United States | en_GB |
dc.publisher.country | Yhdysvallat (USA) | fi_FI |
dc.publisher.country-code | US | |
dc.publisher.place | Hoboken | |
dc.relation.doi | 10.1111/bcp.15485 | |
dc.relation.ispartofjournal | British Journal of Clinical Pharmacology | |
dc.year.issued | 2022 | |