Genetic variants associated with gastrointestinal symptoms in Fabry disease
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...
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| Veröffentlicht in: | Oncotarget 2016-12, Vol.7 (52), p.85895-85904 |
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| creator | Di Martino, Maria Teresa Scionti, Francesca Sestito, Simona Nicoletti, Angela Arbitrio, Mariamena Hiram Guzzi, Pietro Talarico, Valentina Altomare, Federica Sanseviero, Maria Teresa Agapito, Giuseppe Pisani, Antonio Riccio, Eleonora Borrelli, Osvaldo Concolino, Daniela Pensabene, Licia |
| description | 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. |
| doi_str_mv | 10.18632/oncotarget.13135 |
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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.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.13135</identifier><identifier>PMID: 27825144</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Adult ; ATP Binding Cassette Subfamily B Member 11 - genetics ; Fabry Disease - complications ; Fabry Disease - genetics ; Female ; Gastrointestinal Diseases - genetics ; Genetic Variation ; Genotyping Techniques ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Precision Medicine ; Research Paper</subject><ispartof>Oncotarget, 2016-12, Vol.7 (52), p.85895-85904</ispartof><rights>Copyright: © 2016 Di Martino et al. 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-b70ef12050a1584dac5b9669feded0efa169d8676eed0906293b0d9d97e0bb2e3</citedby><cites>FETCH-LOGICAL-c356t-b70ef12050a1584dac5b9669feded0efa169d8676eed0906293b0d9d97e0bb2e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349883/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349883/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27825144$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Di Martino, Maria Teresa</creatorcontrib><creatorcontrib>Scionti, Francesca</creatorcontrib><creatorcontrib>Sestito, Simona</creatorcontrib><creatorcontrib>Nicoletti, Angela</creatorcontrib><creatorcontrib>Arbitrio, Mariamena</creatorcontrib><creatorcontrib>Hiram Guzzi, Pietro</creatorcontrib><creatorcontrib>Talarico, Valentina</creatorcontrib><creatorcontrib>Altomare, Federica</creatorcontrib><creatorcontrib>Sanseviero, Maria Teresa</creatorcontrib><creatorcontrib>Agapito, Giuseppe</creatorcontrib><creatorcontrib>Pisani, Antonio</creatorcontrib><creatorcontrib>Riccio, Eleonora</creatorcontrib><creatorcontrib>Borrelli, Osvaldo</creatorcontrib><creatorcontrib>Concolino, Daniela</creatorcontrib><creatorcontrib>Pensabene, Licia</creatorcontrib><title>Genetic variants associated with gastrointestinal symptoms in Fabry disease</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>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.</description><subject>Adult</subject><subject>ATP Binding Cassette Subfamily B Member 11 - genetics</subject><subject>Fabry Disease - complications</subject><subject>Fabry Disease - genetics</subject><subject>Female</subject><subject>Gastrointestinal Diseases - genetics</subject><subject>Genetic Variation</subject><subject>Genotyping Techniques</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Precision Medicine</subject><subject>Research Paper</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1PAjEQbYxGiPIDvJg9ellst9tlezExRNBI4kXPzex2gJrdFtuC4d-7AUScy5vJzLz5eITcMDpkZcGze2drF8EvMA4ZZ1yckT6TuUwzIfj5id8jgxA-aWciH5WZvCS9rEPB8rxPXqdoMZo62YA3YGNIIARXG4iok28Tl8kCQvTO2IghGgtNErbtKro2JMYmE6j8NtEmIAS8JhdzaAIODnhFPiZP7-PndPY2fRk_ztKaiyKm1YjinGVUUGCizDXUopJFIeeoUXcpYIXUZTEqsAslLTLJK6qlliOkVZUhvyIPe97VumpR12ijh0atvGnBb5UDo_5nrFmqhdsowXNZlrwjuDsQePe17u5SrQk1Ng1YdOugWMklY5znoitl-9LauxA8zo9jGFU7HdSfDmqnQ9dze7rfseP36_wHmR-JfA</recordid><startdate>20161227</startdate><enddate>20161227</enddate><creator>Di Martino, Maria Teresa</creator><creator>Scionti, Francesca</creator><creator>Sestito, Simona</creator><creator>Nicoletti, Angela</creator><creator>Arbitrio, Mariamena</creator><creator>Hiram Guzzi, Pietro</creator><creator>Talarico, Valentina</creator><creator>Altomare, Federica</creator><creator>Sanseviero, Maria Teresa</creator><creator>Agapito, Giuseppe</creator><creator>Pisani, Antonio</creator><creator>Riccio, Eleonora</creator><creator>Borrelli, Osvaldo</creator><creator>Concolino, Daniela</creator><creator>Pensabene, Licia</creator><general>Impact Journals LLC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20161227</creationdate><title>Genetic variants associated with gastrointestinal symptoms in Fabry disease</title><author>Di Martino, Maria Teresa ; Scionti, Francesca ; Sestito, Simona ; Nicoletti, Angela ; Arbitrio, Mariamena ; Hiram Guzzi, Pietro ; Talarico, Valentina ; Altomare, Federica ; Sanseviero, Maria Teresa ; Agapito, Giuseppe ; Pisani, Antonio ; Riccio, Eleonora ; Borrelli, Osvaldo ; Concolino, Daniela ; Pensabene, Licia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-b70ef12050a1584dac5b9669feded0efa169d8676eed0906293b0d9d97e0bb2e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>ATP Binding Cassette Subfamily B Member 11 - genetics</topic><topic>Fabry Disease - complications</topic><topic>Fabry Disease - genetics</topic><topic>Female</topic><topic>Gastrointestinal Diseases - genetics</topic><topic>Genetic Variation</topic><topic>Genotyping Techniques</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Precision Medicine</topic><topic>Research Paper</topic><toplevel>online_resources</toplevel><creatorcontrib>Di Martino, Maria Teresa</creatorcontrib><creatorcontrib>Scionti, Francesca</creatorcontrib><creatorcontrib>Sestito, Simona</creatorcontrib><creatorcontrib>Nicoletti, Angela</creatorcontrib><creatorcontrib>Arbitrio, Mariamena</creatorcontrib><creatorcontrib>Hiram Guzzi, Pietro</creatorcontrib><creatorcontrib>Talarico, Valentina</creatorcontrib><creatorcontrib>Altomare, Federica</creatorcontrib><creatorcontrib>Sanseviero, Maria Teresa</creatorcontrib><creatorcontrib>Agapito, Giuseppe</creatorcontrib><creatorcontrib>Pisani, Antonio</creatorcontrib><creatorcontrib>Riccio, Eleonora</creatorcontrib><creatorcontrib>Borrelli, Osvaldo</creatorcontrib><creatorcontrib>Concolino, Daniela</creatorcontrib><creatorcontrib>Pensabene, Licia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Di Martino, Maria Teresa</au><au>Scionti, Francesca</au><au>Sestito, Simona</au><au>Nicoletti, Angela</au><au>Arbitrio, Mariamena</au><au>Hiram Guzzi, Pietro</au><au>Talarico, Valentina</au><au>Altomare, Federica</au><au>Sanseviero, Maria Teresa</au><au>Agapito, Giuseppe</au><au>Pisani, Antonio</au><au>Riccio, Eleonora</au><au>Borrelli, Osvaldo</au><au>Concolino, Daniela</au><au>Pensabene, Licia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic variants associated with gastrointestinal symptoms in Fabry disease</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2016-12-27</date><risdate>2016</risdate><volume>7</volume><issue>52</issue><spage>85895</spage><epage>85904</epage><pages>85895-85904</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>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.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>27825144</pmid><doi>10.18632/oncotarget.13135</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult ATP Binding Cassette Subfamily B Member 11 - genetics Fabry Disease - complications Fabry Disease - genetics Female Gastrointestinal Diseases - genetics Genetic Variation Genotyping Techniques Humans Male Middle Aged Polymorphism, Single Nucleotide Precision Medicine Research Paper |
| title | Genetic variants associated with gastrointestinal symptoms in Fabry disease |
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