Title |
CYP2C8 and SLCO1B1 Variants and Therapeutic Response to Thiazolidinediones in Patients With Type 2 Diabetes
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Published in |
Diabetes Care, June 2016
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DOI | 10.2337/dc15-2464 |
Pubmed ID | |
Authors |
Adem Y. Dawed, Louise Donnelly, Roger Tavendale, Fiona Carr, Graham Leese, Colin N.A. Palmer, Ewan R. Pearson, Kaixin Zhou |
Abstract |
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. 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. 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. 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. |
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United States | 1 | 100% |
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Members of the public | 1 | 100% |
Mendeley readers
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Readers by professional status | Count | As % |
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Researcher | 9 | 19% |
Student > Bachelor | 6 | 13% |
Student > Master | 4 | 8% |
Student > Doctoral Student | 3 | 6% |
Professor > Associate Professor | 3 | 6% |
Other | 8 | 17% |
Unknown | 15 | 31% |
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Agricultural and Biological Sciences | 2 | 4% |
Environmental Science | 1 | 2% |
Other | 3 | 6% |
Unknown | 18 | 38% |