Research Papers:

Genetic variants associated with Fabry disease progression despite enzyme replacement therapy

Francesca Scionti, Maria Teresa Di Martino _, Simona Sestito, Angela Nicoletti, Francesca Falvo, Katia Roppa, Mariamena Arbitrio, Pietro Hiram Guzzi, Giuseppe Agapito, Antonio Pisani, Eleonora Riccio, Daniela Concolino and Licia Pensabene

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Oncotarget. 2017; 8:107558-107564. https://doi.org/10.18632/oncotarget.22505

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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

Correspondence to:

Maria Teresa Di Martino, email: [email protected]

Licia Pensabene, email: [email protected]

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.

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