Department of Medicine, Division of Genetic Medicine and Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
Pharmacogenomics J. 2020 Dec;20(6):831-839. doi: 10.1038/s41397-020-0171-4. Epub 2020 Jun 5.
Hypoglycemia is a common complication among type 2 diabetes mellitus (T2DM) patients receiving sulfonylurea therapy. The aim of this study was to determine if genetic contributions to sulfonylurea pharmacokinetics or pharmacodynamics substantially affect the risk of hypoglycemia in these patients. In a retrospective case-control study in European American patients with T2DM, we examined the potential association between CYP2C9 reduced-function variants and sulfonylurea-related hypoglycemia. We also explored the relationship between sulfonylurea-related hypoglycemia and several candidate genetic variants previously reported to alter the response to sulfonylureas. We detected no evidence of association between CYP2C9 reduced-function alleles or any of the candidate genetic variants and sulfonylurea-related hypoglycemia. In conclusion, we identified no clinically significant predictors of hypoglycemia among genes associated with sulfonylurea pharmacokinetics or pharmacodynamics.
低血糖症是接受磺酰脲类治疗的 2 型糖尿病(T2DM)患者常见的并发症。本研究旨在确定磺酰脲类药代动力学或药效学的遗传因素是否会显著影响这些患者发生低血糖症的风险。在一项对欧洲裔 2 型糖尿病患者的回顾性病例对照研究中,我们检测了 CYP2C9 功能降低变异体与磺酰脲类相关低血糖症之间的潜在关联。我们还探讨了磺酰脲类相关低血糖症与先前报道可改变磺酰脲类药物反应的几种候选遗传变异体之间的关系。我们没有发现 CYP2C9 功能降低等位基因或任何候选遗传变异体与磺酰脲类相关低血糖症之间存在关联的证据。总之,我们在与磺酰脲类药代动力学或药效学相关的基因中未发现低血糖症的临床显著预测因子。