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- Title
CYP2C8 and SLCO1B1 Variants and Therapeutic Response to Thiazolidinediones in Patients With Type 2 Diabetes.
- Authors
Dawed, Adem Y.; Donnelly, Louise; Tavendale, Roger; Carr, Fiona; Leese, Graham; Palmer, Colin N. A.; Pearson, Ewan R.; Kaixin Zhou; Zhou, Kaixin
- Abstract
<bold>Objective: </bold>Thiazolidinediones (TZDs) are putatively transported into the liver by OATP1B1 (encoded by SLCO1B1) and metabolized by CYP450 2C8 enzyme (encoded by CYP2C8). While CYP2C8*3 has been shown to alter TZD pharmacokinetics, it has not been shown to alter efficacy.<bold>Research Design and Methods: </bold>We genotyped 833 Scottish patients with type 2 diabetes treated with pioglitazone or rosiglitazone and jointly investigated association of variants in these two genes with therapeutic outcome.<bold>Results: </bold>The CYP2C8*3 variant was associated with reduced glycemic response to rosiglitazone (P = 0.01) and less weight gain (P = 0.02). The SLCO1B1 521T>C variant was associated with enhanced glycemic response to rosiglitazone (P = 0.04). The super responders defined by combined genotypes at CYP2C8 and SLCO1B1 had a 0.39% (4 mmol/mol) greater HbA1c reduction (P = 0.006) than the poor responders. Neither of the variants had a significant impact on pioglitazone response.<bold>Conclusions: </bold>These results show that variants in CYP2C8 and SLCO1B1 have a large clinical impact on the therapeutic response to rosiglitazone and highlight the importance of studying transporter and metabolizing genes together in pharmacogenetics.
- Subjects
SCOTLAND; PEOPLE with diabetes; THIAZOLIDINEDIONES; PHARMACOKINETICS; GLYCEMIC control; ROSIGLITAZONE; HYPOGLYCEMIC agents; BLOOD sugar; GENETIC polymorphisms; TYPE 2 diabetes; OXIDOREDUCTASES; PHARMACOGENOMICS; REGRESSION analysis; RESEARCH funding; WHITE people; TREATMENT effectiveness; GENOTYPES; THERAPEUTICS
- Publication
Diabetes Care, 2016, Vol 39, Issue 11, p1902
- ISSN
0149-5992
- Publication type
journal article
- DOI
10.2337/dc15-2464