RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease

Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses in variable length of the intestine. This study investigated the influence and a possible modifying function of RET proto-oncogene's single nucleotide polymorphisms (SNPs) and haplotypes in the develo...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2014-06, Vol.9 (6), p.e98957-e98957
Hauptverfasser: Vaclavikova, Eliska, Dvorakova, Sarka, Skaba, Richard, Pos, Lucie, Sykorova, Vlasta, Halkova, Tereza, Vcelak, Josef, Bendlova, Bela
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page e98957
container_issue 6
container_start_page e98957
container_title PloS one
container_volume 9
creator Vaclavikova, Eliska
Dvorakova, Sarka
Skaba, Richard
Pos, Lucie
Sykorova, Vlasta
Halkova, Tereza
Vcelak, Josef
Bendlova, Bela
description Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses in variable length of the intestine. This study investigated the influence and a possible modifying function of RET proto-oncogene's single nucleotide polymorphisms (SNPs) and haplotypes in the development and phenotype of the disease in Czech patients. Genotyping of 14 SNPs was performed using TaqMan Genotyping Assays and direct sequencing. The frequencies of SNPs and generated haplotypes were statistically evaluated using chi-square test and the association with the risk of HSCR was estimated by odds ratio. SNP analysis revealed significant differences in frequencies of 11 polymorphic RET variants between 162 HSCR patients and 205 unaffected controls. Particularly variant alleles of rs1864410, rs2435357, rs2506004 (intron 1), rs1800858 (exon 2), rs1800861 (exon 13), and rs2565200 (intron 19) were strongly associated with increased risk of HSCR (p
doi_str_mv 10.1371/journal.pone.0098957
format Article
fullrecord <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1532653305</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A416975561</galeid><doaj_id>oai_doaj_org_article_751acbf3bec54d5083d9e5825014d151</doaj_id><sourcerecordid>A416975561</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-d7944550aa04e800086cb7542376ed513e3a664923b8ed9a11fb57aecea549673</originalsourceid><addsrcrecordid>eNqNk01v1DAQhiMEomXhHyCIhITgsIsdfyS5IFWrQleqVKkULhysWWeycZWNUzspLL8ep5tWG9QD8iG287yvZ8aeKHpNyYKylH66tr1roF60tsEFIXmWi_RJdExzlsxlQtjTg_lR9ML7a0IEy6R8Hh0lPMtTmsjj6Ofl6VV8C85A0_kYmiKuoK1tt2sxrKDeeeNj08QQa1tZ18W2jJd_UFdxC53BQfTLdFV8ZpzXlW9d32ziwngEjy-jZyXUHl-N31n0_cvp1fJsfn7xdbU8OZ9rmSfdvEhzzoUgAIRjRgjJpF6ngicslVgIypCBlDxP2DrDIgdKy7VIATWC4LlM2Sx6u_cNgXs11sUrKlgiBWMh61m02hOFhWvVOrMFt1MWjLrbsG6jwHVG16hSQUGvS7ZGLXghSMaKHEWWCEJ5QUM0s-jzeFq_3mKhQw0c1BPT6Z_GVGpjbxUnXGREBoMPo4GzNz36Tm2N11jX0KDt7-LmlIQxxP3uH_Tx7EZqAyEB05Q2nKsHU3XCqcxTIeQQ9-IRKowCt0aHR1SasD8RfJwIAtPh724Dvfdq9e3y_9mLH1P2_QFbIdRd5W3dd8Y2fgryPaid9d5h-VBkStTQA_fVUEMPqLEHguzN4QU9iO4fPfsLAyEAQg</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1532653305</pqid></control><display><type>article</type><title>RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Vaclavikova, Eliska ; Dvorakova, Sarka ; Skaba, Richard ; Pos, Lucie ; Sykorova, Vlasta ; Halkova, Tereza ; Vcelak, Josef ; Bendlova, Bela</creator><contributor>Miao, Xiaoping</contributor><creatorcontrib>Vaclavikova, Eliska ; Dvorakova, Sarka ; Skaba, Richard ; Pos, Lucie ; Sykorova, Vlasta ; Halkova, Tereza ; Vcelak, Josef ; Bendlova, Bela ; Miao, Xiaoping</creatorcontrib><description>Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses in variable length of the intestine. This study investigated the influence and a possible modifying function of RET proto-oncogene's single nucleotide polymorphisms (SNPs) and haplotypes in the development and phenotype of the disease in Czech patients. Genotyping of 14 SNPs was performed using TaqMan Genotyping Assays and direct sequencing. The frequencies of SNPs and generated haplotypes were statistically evaluated using chi-square test and the association with the risk of HSCR was estimated by odds ratio. SNP analysis revealed significant differences in frequencies of 11 polymorphic RET variants between 162 HSCR patients and 205 unaffected controls. Particularly variant alleles of rs1864410, rs2435357, rs2506004 (intron 1), rs1800858 (exon 2), rs1800861 (exon 13), and rs2565200 (intron 19) were strongly associated with increased risk of HSCR (p&lt;0.00000) and were over-represented in males vs. females. Conversely, variant alleles of rs1800860, rs1799939 and rs1800863 (exons 7, 11, 15) had a protective role. The haploblock comprising variants in intron 1 and exon 2 was constructed. It represented a high risk of HSCR, however, the influence of other variants was also found after pruning from effect of this haploblock. Clustering patients according to genotype status in haploblock revealed a strong co-segregation with several SNPs and pointed out the differences between long and short form of HSCR. This study involved a large number of SNPs along the entire RET proto-oncogene with demonstration of their risk/protective role also in haplotype and diplotype analysis in the Czech population. The influence of some variant alleles on the aggressiveness of the disease and their role in gender manifestation differences was found. These data contribute to worldwide knowledge of the genetics of HSCR.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0098957</identifier><identifier>PMID: 24897126</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alleles ; Analysis ; Biology and Life Sciences ; Case-Control Studies ; Chromosomes ; Clustering ; Congenital diseases ; Czech Republic ; Endocrinology ; Exons ; Female ; Females ; Follow-Up Studies ; Gene expression ; Genetic Markers ; Genetics ; Genotype ; Genotyping ; Haplotypes ; Haplotypes - genetics ; Hirschsprung Disease - genetics ; Hirschsprung's disease ; Humans ; Intestine ; Kinases ; Male ; Males ; Medicine and Health Sciences ; Mutation ; Pathogenesis ; Patients ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide - genetics ; Population genetics ; Prognosis ; Prospective Studies ; Proto-Oncogene Proteins c-ret - genetics ; Pruning ; Ret protein ; Retrospective Studies ; Risk ; Sequence Analysis, DNA ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Statistical tests ; Thyroid cancer</subject><ispartof>PloS one, 2014-06, Vol.9 (6), p.e98957-e98957</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Vaclavikova et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Vaclavikova et al 2014 Vaclavikova et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-d7944550aa04e800086cb7542376ed513e3a664923b8ed9a11fb57aecea549673</citedby><cites>FETCH-LOGICAL-c692t-d7944550aa04e800086cb7542376ed513e3a664923b8ed9a11fb57aecea549673</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/PMC4045806/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045806/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24897126$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Miao, Xiaoping</contributor><creatorcontrib>Vaclavikova, Eliska</creatorcontrib><creatorcontrib>Dvorakova, Sarka</creatorcontrib><creatorcontrib>Skaba, Richard</creatorcontrib><creatorcontrib>Pos, Lucie</creatorcontrib><creatorcontrib>Sykorova, Vlasta</creatorcontrib><creatorcontrib>Halkova, Tereza</creatorcontrib><creatorcontrib>Vcelak, Josef</creatorcontrib><creatorcontrib>Bendlova, Bela</creatorcontrib><title>RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses in variable length of the intestine. This study investigated the influence and a possible modifying function of RET proto-oncogene's single nucleotide polymorphisms (SNPs) and haplotypes in the development and phenotype of the disease in Czech patients. Genotyping of 14 SNPs was performed using TaqMan Genotyping Assays and direct sequencing. The frequencies of SNPs and generated haplotypes were statistically evaluated using chi-square test and the association with the risk of HSCR was estimated by odds ratio. SNP analysis revealed significant differences in frequencies of 11 polymorphic RET variants between 162 HSCR patients and 205 unaffected controls. Particularly variant alleles of rs1864410, rs2435357, rs2506004 (intron 1), rs1800858 (exon 2), rs1800861 (exon 13), and rs2565200 (intron 19) were strongly associated with increased risk of HSCR (p&lt;0.00000) and were over-represented in males vs. females. Conversely, variant alleles of rs1800860, rs1799939 and rs1800863 (exons 7, 11, 15) had a protective role. The haploblock comprising variants in intron 1 and exon 2 was constructed. It represented a high risk of HSCR, however, the influence of other variants was also found after pruning from effect of this haploblock. Clustering patients according to genotype status in haploblock revealed a strong co-segregation with several SNPs and pointed out the differences between long and short form of HSCR. This study involved a large number of SNPs along the entire RET proto-oncogene with demonstration of their risk/protective role also in haplotype and diplotype analysis in the Czech population. The influence of some variant alleles on the aggressiveness of the disease and their role in gender manifestation differences was found. These data contribute to worldwide knowledge of the genetics of HSCR.</description><subject>Alleles</subject><subject>Analysis</subject><subject>Biology and Life Sciences</subject><subject>Case-Control Studies</subject><subject>Chromosomes</subject><subject>Clustering</subject><subject>Congenital diseases</subject><subject>Czech Republic</subject><subject>Endocrinology</subject><subject>Exons</subject><subject>Female</subject><subject>Females</subject><subject>Follow-Up Studies</subject><subject>Gene expression</subject><subject>Genetic Markers</subject><subject>Genetics</subject><subject>Genotype</subject><subject>Genotyping</subject><subject>Haplotypes</subject><subject>Haplotypes - genetics</subject><subject>Hirschsprung Disease - genetics</subject><subject>Hirschsprung's disease</subject><subject>Humans</subject><subject>Intestine</subject><subject>Kinases</subject><subject>Male</subject><subject>Males</subject><subject>Medicine and Health Sciences</subject><subject>Mutation</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Population genetics</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Proto-Oncogene Proteins c-ret - genetics</subject><subject>Pruning</subject><subject>Ret protein</subject><subject>Retrospective Studies</subject><subject>Risk</subject><subject>Sequence Analysis, DNA</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistical tests</subject><subject>Thyroid cancer</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk01v1DAQhiMEomXhHyCIhITgsIsdfyS5IFWrQleqVKkULhysWWeycZWNUzspLL8ep5tWG9QD8iG287yvZ8aeKHpNyYKylH66tr1roF60tsEFIXmWi_RJdExzlsxlQtjTg_lR9ML7a0IEy6R8Hh0lPMtTmsjj6Ofl6VV8C85A0_kYmiKuoK1tt2sxrKDeeeNj08QQa1tZ18W2jJd_UFdxC53BQfTLdFV8ZpzXlW9d32ziwngEjy-jZyXUHl-N31n0_cvp1fJsfn7xdbU8OZ9rmSfdvEhzzoUgAIRjRgjJpF6ngicslVgIypCBlDxP2DrDIgdKy7VIATWC4LlM2Sx6u_cNgXs11sUrKlgiBWMh61m02hOFhWvVOrMFt1MWjLrbsG6jwHVG16hSQUGvS7ZGLXghSMaKHEWWCEJ5QUM0s-jzeFq_3mKhQw0c1BPT6Z_GVGpjbxUnXGREBoMPo4GzNz36Tm2N11jX0KDt7-LmlIQxxP3uH_Tx7EZqAyEB05Q2nKsHU3XCqcxTIeQQ9-IRKowCt0aHR1SasD8RfJwIAtPh724Dvfdq9e3y_9mLH1P2_QFbIdRd5W3dd8Y2fgryPaid9d5h-VBkStTQA_fVUEMPqLEHguzN4QU9iO4fPfsLAyEAQg</recordid><startdate>20140604</startdate><enddate>20140604</enddate><creator>Vaclavikova, Eliska</creator><creator>Dvorakova, Sarka</creator><creator>Skaba, Richard</creator><creator>Pos, Lucie</creator><creator>Sykorova, Vlasta</creator><creator>Halkova, Tereza</creator><creator>Vcelak, Josef</creator><creator>Bendlova, Bela</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140604</creationdate><title>RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease</title><author>Vaclavikova, Eliska ; Dvorakova, Sarka ; Skaba, Richard ; Pos, Lucie ; Sykorova, Vlasta ; Halkova, Tereza ; Vcelak, Josef ; Bendlova, Bela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-d7944550aa04e800086cb7542376ed513e3a664923b8ed9a11fb57aecea549673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Alleles</topic><topic>Analysis</topic><topic>Biology and Life Sciences</topic><topic>Case-Control Studies</topic><topic>Chromosomes</topic><topic>Clustering</topic><topic>Congenital diseases</topic><topic>Czech Republic</topic><topic>Endocrinology</topic><topic>Exons</topic><topic>Female</topic><topic>Females</topic><topic>Follow-Up Studies</topic><topic>Gene expression</topic><topic>Genetic Markers</topic><topic>Genetics</topic><topic>Genotype</topic><topic>Genotyping</topic><topic>Haplotypes</topic><topic>Haplotypes - genetics</topic><topic>Hirschsprung Disease - genetics</topic><topic>Hirschsprung's disease</topic><topic>Humans</topic><topic>Intestine</topic><topic>Kinases</topic><topic>Male</topic><topic>Males</topic><topic>Medicine and Health Sciences</topic><topic>Mutation</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Population genetics</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Proto-Oncogene Proteins c-ret - genetics</topic><topic>Pruning</topic><topic>Ret protein</topic><topic>Retrospective Studies</topic><topic>Risk</topic><topic>Sequence Analysis, DNA</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Statistical tests</topic><topic>Thyroid cancer</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vaclavikova, Eliska</creatorcontrib><creatorcontrib>Dvorakova, Sarka</creatorcontrib><creatorcontrib>Skaba, Richard</creatorcontrib><creatorcontrib>Pos, Lucie</creatorcontrib><creatorcontrib>Sykorova, Vlasta</creatorcontrib><creatorcontrib>Halkova, Tereza</creatorcontrib><creatorcontrib>Vcelak, Josef</creatorcontrib><creatorcontrib>Bendlova, Bela</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vaclavikova, Eliska</au><au>Dvorakova, Sarka</au><au>Skaba, Richard</au><au>Pos, Lucie</au><au>Sykorova, Vlasta</au><au>Halkova, Tereza</au><au>Vcelak, Josef</au><au>Bendlova, Bela</au><au>Miao, Xiaoping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-06-04</date><risdate>2014</risdate><volume>9</volume><issue>6</issue><spage>e98957</spage><epage>e98957</epage><pages>e98957-e98957</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses in variable length of the intestine. This study investigated the influence and a possible modifying function of RET proto-oncogene's single nucleotide polymorphisms (SNPs) and haplotypes in the development and phenotype of the disease in Czech patients. Genotyping of 14 SNPs was performed using TaqMan Genotyping Assays and direct sequencing. The frequencies of SNPs and generated haplotypes were statistically evaluated using chi-square test and the association with the risk of HSCR was estimated by odds ratio. SNP analysis revealed significant differences in frequencies of 11 polymorphic RET variants between 162 HSCR patients and 205 unaffected controls. Particularly variant alleles of rs1864410, rs2435357, rs2506004 (intron 1), rs1800858 (exon 2), rs1800861 (exon 13), and rs2565200 (intron 19) were strongly associated with increased risk of HSCR (p&lt;0.00000) and were over-represented in males vs. females. Conversely, variant alleles of rs1800860, rs1799939 and rs1800863 (exons 7, 11, 15) had a protective role. The haploblock comprising variants in intron 1 and exon 2 was constructed. It represented a high risk of HSCR, however, the influence of other variants was also found after pruning from effect of this haploblock. Clustering patients according to genotype status in haploblock revealed a strong co-segregation with several SNPs and pointed out the differences between long and short form of HSCR. This study involved a large number of SNPs along the entire RET proto-oncogene with demonstration of their risk/protective role also in haplotype and diplotype analysis in the Czech population. The influence of some variant alleles on the aggressiveness of the disease and their role in gender manifestation differences was found. These data contribute to worldwide knowledge of the genetics of HSCR.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24897126</pmid><doi>10.1371/journal.pone.0098957</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2014-06, Vol.9 (6), p.e98957-e98957
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1532653305
source MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry
subjects Alleles
Analysis
Biology and Life Sciences
Case-Control Studies
Chromosomes
Clustering
Congenital diseases
Czech Republic
Endocrinology
Exons
Female
Females
Follow-Up Studies
Gene expression
Genetic Markers
Genetics
Genotype
Genotyping
Haplotypes
Haplotypes - genetics
Hirschsprung Disease - genetics
Hirschsprung's disease
Humans
Intestine
Kinases
Male
Males
Medicine and Health Sciences
Mutation
Pathogenesis
Patients
Polymerase Chain Reaction
Polymorphism, Single Nucleotide - genetics
Population genetics
Prognosis
Prospective Studies
Proto-Oncogene Proteins c-ret - genetics
Pruning
Ret protein
Retrospective Studies
Risk
Sequence Analysis, DNA
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Statistical tests
Thyroid cancer
title RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T06%3A23%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=RET%20variants%20and%20haplotype%20analysis%20in%20a%20cohort%20of%20Czech%20patients%20with%20Hirschsprung%20disease&rft.jtitle=PloS%20one&rft.au=Vaclavikova,%20Eliska&rft.date=2014-06-04&rft.volume=9&rft.issue=6&rft.spage=e98957&rft.epage=e98957&rft.pages=e98957-e98957&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0098957&rft_dat=%3Cgale_plos_%3EA416975561%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1532653305&rft_id=info:pmid/24897126&rft_galeid=A416975561&rft_doaj_id=oai_doaj_org_article_751acbf3bec54d5083d9e5825014d151&rfr_iscdi=true