Scionti Francesca, Di Martino Maria Teresa, Sestito Simona, Nicoletti Angela, Falvo Francesca, Roppa Katia, Arbitrio Mariamena, Guzzi Pietro Hiram, Agapito Giuseppe, Pisani Antonio, Riccio Eleonora, Concolino Daniela, Pensabene Licia
Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, Catanzaro, Italy.
Department of Medical and Surgical Sciences Pediatric Unit, Magna Graecia University, Catanzaro, Italy.
Oncotarget. 2017 Nov 18;8(64):107558-107564. doi: 10.18632/oncotarget.22505. eCollection 2017 Dec 8.
Enzyme replacement therapy (ERT) has been widely used for the treatment of Fabry disease, a rare X-linked recessive disorder due to absent or reduced activity of lysosomal enzyme α-galactosidase A. It is still unclear why some patients under ERT show disease progression typically with renal, cardiovascular and cerebrovascular dysfunctions. Here, we investigated the involvement of drug absorption, distribution, metabolism, and excretion gene variants in response variability to ERT, genotyping 37 patients with the Affymetrix Drug Metabolizing Enzyme and Transporters (DMET) Plus microarray. We found three single nucleotide polymorphisms in human alcohol dehydrogenase (ADH)4 gene (rs1126670, rs1126671, rs2032349) and one in ADH5 gene (rs2602836) associated with disease progression ( < 0.05). Our data provide a basic tool for identification of patient with ERT non-response risk that may represent a framework for personalized treatment of this rare disease.
酶替代疗法（ERT）已被广泛用于治疗法布里病，这是一种罕见的X连锁隐性疾病，由于溶酶体酶α-半乳糖苷酶A缺乏或活性降低所致。目前仍不清楚为什么一些接受ERT治疗的患者会出现疾病进展，通常伴有肾脏、心血管和脑血管功能障碍。在此，我们研究了药物吸收、分布、代谢和排泄基因变异在ERT反应变异性中的作用，使用Affymetrix药物代谢酶和转运体（DMET）Plus微阵列对37例患者进行基因分型。我们发现人类乙醇脱氢酶（ADH）4基因中的三个单核苷酸多态性（rs1126670、rs1126671、rs2032349）和ADH5基因中的一个（rs2602836）与疾病进展相关（P<0.05）。我们的数据为识别有ERT无反应风险的患者提供了一个基本工具，这可能为这种罕见疾病的个性化治疗提供一个框架。
