Genetic variants associated with Fabry disease progression despite enzyme replacement therapy
Metrics: PDF 726 views | HTML 1133 views | ?
Francesca Scionti1,*, Maria Teresa Di Martino1,*, Simona Sestito2, Angela Nicoletti2, Francesca Falvo2, Katia Roppa2, Mariamena Arbitrio3, Pietro Hiram Guzzi4, Giuseppe Agapito4, Antonio Pisani5, Eleonora Riccio5, Daniela Concolino2,# and Licia Pensabene2,#
1Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, Catanzaro, Italy
2Department of Medical and Surgical Sciences Pediatric Unit, Magna Graecia University, Catanzaro, Italy
3ISN-CNR, Roccelletta di Borgia, Catanzaro, Italy
4Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
5Department of Nephrology, University Federico II, Naples, Italy
*These authors contributed equally to the work
#These authors contributed equally to this work and share senior authorship
Maria Teresa Di Martino, email: firstname.lastname@example.org
Licia Pensabene, email: email@example.com
Keywords: Fabry disease; enzyme replacement therapy; DMET; ADH genes; oxidative stress
Received: August 24, 2017 Accepted: October 29, 2017 Published: November 18, 2017
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 (p < 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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.