Jaja Cheedy, Barrett Nadine, Patel Niren, Lyon Matt, Xu Hongyan, Kutlar Abdullah
1 College of Nursing, University of Cincinnati , Cincinnati, Ohio.
2 Department of Medicine, Georgia Regents University , Augusta, Georgia .
Genet Test Mol Biomarkers. 2016 Oct;20(10):609-615. doi: 10.1089/gtmb.2016.0001. Epub 2016 Aug 23.
Interindividual variability in drug response and adverse effects have been described for proton pump inhibitors, anticonvulsants, selective serotonin reuptake inhibitors, tricyclic antidepressants, and anti-infectives, but little is known about the safety and efficacy of these medications in patients with sickle cell disease (SCD). We genotyped the CYP2C19 gene which has been implicated in the metabolism of these drugs in an SCD patient cohort to determine the frequencies of reduced function, increased function, or complete loss-of-function variants.
DNAs from 165 unrelated SCD patients were genotyped for nine CYP2C19 (*2, *3, *4, *5, *6, *7,*8, *12, and *17) alleles using the iPLEX ADME PGx multiplex panel.
Three CYP2C19 alleles (*2, *12, and *17) were detected with the following frequencies: 0.209, 0.006, and 0.236, respectively. The predicted phenotype frequencies were distributed as extensive (31.5%), intermediate (24.8%), poor (5.5%), ultrarapid (30.3%), and unknown metabolizers (7.9%).
Prognostic genotyping is potentially useful for identifying SCD patients with allelic variants linked to proven clinical pharmacokinetic consequences for several drugs metabolized by the CYP2C19 gene. However, the main challenge to implementing a genetics-guided prescribing practice is ensuring concordance between CYP2C19 genotypes and metabolic phenotypes in SCD patients.
质子泵抑制剂、抗惊厥药、选择性5-羟色胺再摄取抑制剂、三环类抗抑郁药及抗感染药的药物反应和不良反应存在个体间差异，但对于这些药物在镰状细胞病（SCD）患者中的安全性和疗效却知之甚少。我们对一个SCD患者队列中参与这些药物代谢的CYP2C19基因进行基因分型，以确定功能降低、功能增强或功能完全丧失变异的频率。
使用iPLEX ADME PGx多重检测板对165名无亲缘关系的SCD患者的DNA进行9种CYP2C19（*2、*3、*4、*5、*6、*7、*8、12和17）等位基因的基因分型。
检测到3种CYP2C19等位基因（*2、12和17），其频率分别为0.209、0.006和0.236。预测的表型频率分布为广泛代谢型（31.5%）、中间代谢型（24.8%）、慢代谢型（5.5%）、超快代谢型（30.3%）和未知代谢型（7.9%）。
预后基因分型对于识别SCD患者中与CYP2C19基因代谢的几种药物已证实的临床药代动力学后果相关的等位基因变异可能有用。然而，实施基因指导的处方实践的主要挑战是确保SCD患者的CYP2C19基因型与代谢表型之间的一致性。
