Research Papers:

Genetic variants associated with gastrointestinal symptoms in Fabry disease

Maria Teresa Di Martino, Francesca Scionti, Simona Sestito, Angela Nicoletti, Mariamena Arbitrio, Pietro Hiram Guzzi, Valentina Talarico, Federica Altomare, Maria Teresa Sanseviero, Giuseppe Agapito, Antonio Pisani, Eleonora Riccio, Osvaldo Borrelli, Daniela Concolino and Licia Pensabene _

PDF  |  HTML  |  How to cite

Oncotarget. 2016; 7:85895-85904. https://doi.org/10.18632/oncotarget.13135

Metrics: PDF 2078 views  |   HTML 2563 views  |   ?  


Maria Teresa Di Martino1,*, Francesca Scionti1,*, Simona Sestito2, Angela Nicoletti2, Mariamena Arbitrio3, Pietro Hiram Guzzi4, Valentina Talarico2, Federica Altomare2, Maria Teresa Sanseviero2, Giuseppe Agapito4, Antonio Pisani5, Eleonora Riccio5, Osvaldo Borrelli6, Daniela Concolino2,**, Licia Pensabene2,6,**

1Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, Catanzaro, 88100 Italy

2Department of Medical and Surgical Sciences, Pediatric Unit, Magna Graecia University, Catanzaro, 88100 Italy

3ISN-CNR, Roccelletta di Borgia, Catanzaro, 88100 Italy

4Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, 88100 Italy

5Departement of Nephrology University Federico II, Naples, 80138 Italy

6Department of Pediatric Gastroenterology, Great Ormond Street Hospital for Sick Children, University College of London (UCL), London, WC1E 6BT, UK

*These authors have contributed equally to this work

**These authors have contributed equally to this work and share senior authorship

Correspondence to:

Licia Pensabene, email: [email protected]

Maria Teresa Di Martino, email: [email protected]

Keywords: Fabry disease, gastrointestinal symptoms, bile acids, DMET, genetic polymorphisms

Received: June 08, 2016     Accepted: October 29, 2016     Published: November 05, 2016


Gastrointestinal symptoms (GIS) are often among the earliest presenting events in Fabry disease (FD), an X-linked lysosomal disorder caused by the deficiency of α-galactosidase A. Despite recent advances in clinical and molecular characterization of FD, the pathophysiology of the GIS is still poorly understood. To shed light either on differential clinical presentation or on intervariability of GIS in FD, we genotyped 1936 genetic markers across 231 genes that encode for drug-metabolizing enzymes and drug transport proteins in 49 FD patients, using the DMET Plus platform. All nine single nucleotide polymorphisms (SNPs) mapped within four genes showed statistically significant differences in genotype frequencies between FD patients who experienced GIS and patients without GIS: ABCB11 (odd ratio (OR) = 18.07, P = 0,0019; OR = 8.21, P = 0,0083; OR=8.21, P = 0,0083; OR = 8.21, P = 0,0083),SLCO1B1 (OR = 9.23, P = 0,0065; OR = 5.08, P = 0,0289; OR = 8.21, P = 0,0083), NR1I3 (OR = 5.40, P = 0,0191) and ABCC5 (OR = 14.44, P = 0,0060). This is the first study that investigates the relationships between genetic heterogeneity in drug absorption, distribution, metabolism and excretion (ADME) related genes and GIS in FD. Our findings provide a novel genetic variant framework which warrants further investigation for precision medicine in FD.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 13135