未经批准:药物遗传学(PGx)小组检测有助于确定类风湿关节炎(RA)患者对甲氨蝶呤(MTX)治疗失败和/或药物不良反应(ADR)的易感性。考虑到提到PGx面板测试在MTX方案中的潜在适用性的文献,我们讨论了一个用MTX治疗的病人,患有ADR,并获得了反应性PGx面板测试。
UNASSIGNED:我们使用了涉及ABC转运蛋白P-糖蛋白(P-gp;基因:ABCB1)的商业PGx面板测试,和乳腺癌耐药蛋白(BCRP;基因:ABCG2),溶质携带者减少叶酸携带者1(RFC1;基因:SLC19A1),和有机阴离子转运多肽1B1(OATP1B1;基因:SLCO1B1),和酶肌苷三磷酸酶(ITPA),和谷胱甘肽转移酶P1(GSTP1)。此外,我们对患者的酶5-氨基咪唑-4-甲酰胺核糖核苷酸甲酰基转移酶(AICAR)/肌苷一磷酸(IMP)环化水解酶(基因名称:ATIC)进行基因分型,γ-谷氨酰水解酶(基因名称:GGH)和亚甲基四氢叶酸还原酶(基因名称:MTHFR)。
未经证实:患者的PGx谱显示SLC19A1、ABCB1和MTHFR的遗传变异,这可能解释了在MTX治疗期间经历的ADR以及MTX可能较低的疗效。根据我们对PGx简介的解释,我们建议患者今后避免使用MTX.
未经证实:MTX途径复杂,这使得对影响新陈代谢的遗传变异的解释具有挑战性。反应性PGx小组测试适用于解释RA患者在MTX治疗期间经历的ADR。然而,PGx引导的MTX治疗在初级治疗中的临床应用仍然有限.为了根据PGx数据推荐MTX,我们需要全基因组关联研究,大型前瞻性多中心研究和PGx研究,分析了MTX的不同多基因单倍型和基因-药物-药物相互作用。
UNASSIGNED: Pharmacogenetic (PGx) panel testing could help to determine the heritable component of a rheumatoid arthritis (RA) patient\'s susceptibility for therapy failure and/or adverse drug reactions (ADRs) from methotrexate (MTX). Considering the literature mentioning the potential applicability of PGx panel testing within MTX regimens, we discuss the
case of a patient who was treated with MTX, suffered from ADRs, and obtained a reactive PGx panel testing.
UNASSIGNED: We used a commercial PGx panel test involving the ABC-transporters P-glycoprotein (P-gp; gene:
ABCB1), and breast cancer resistance protein (BCRP; gene: ABCG2), the solute carriers reduced folate carrier 1 (RFC1; gene: SLC19A1), and organic anion transporting polypeptide 1B1 (OATP1B1; gene: SLCO1B1), and the enzymes inosine triphosphatase (ITPA), and glutathione transferase P1 (GSTP1). In addition, we genotyped the patient for the enzymes 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICAR)/inosine monophosphate (IMP) cyclohydrolase (gene name: ATIC), gamma-glutamyl hydrolase (gene name: GGH) and methylenetetrahydrofolate reductase (gene name: MTHFR).
UNASSIGNED: The PGx profile of the patient revealed genetic variants in SLC19A1,
ABCB1, and MTHFR, which may explain the ADRs experienced during the treatment with MTX and a potentially lower efficacy of MTX. Based on our interpretation of the PGx profile, we recommended the patient to avoid MTX in the future.
UNASSIGNED: The MTX pathway is complex, which makes the interpretation of genetic variants affecting metabolism challenging. A reactive PGx panel test was applicable to explain ADRs experienced during MTX treatment for a patient with RA. However, the clinical utility of PGx-guided MTX treatment in a primary care setting is still limited. In order to base a recommendation for MTX on PGx data, we need genome-wide association studies, large prospective multicenter studies and PGx studies, which analyze different multi-gene haplotypes and gene-drug-drug interactions for MTX.