Genetic variation in the familial Mediterranean fever gene (MEFV) and risk for Crohn's disease and ulcerative colitis
The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has been shown to interact with the gene product of NLRP3, NALP3/cryopyrin, also an important active member of the inflamma...
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| creator | Villani, Alexandra-Chloé Lemire, Mathieu Louis, Edouard Silverberg, Mark S Collette, Catherine Fortin, Geneviève Nimmo, Elaine R Renaud, Yannick Brunet, Sébastien Libioulle, Cécile Belaiche, Jacques Bitton, Alain Gaudet, Daniel Cohen, Albert Langelier, Diane Rioux, John D Arnott, Ian D R Wild, Gary E Rutgeerts, Paul Satsangi, Jack Vermeire, Séverine Hudson, Thomas J Franchimont, Denis |
| description | The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has been shown to interact with the gene product of NLRP3, NALP3/cryopyrin, also an important active member of the inflammasome. The NLRP3 region was recently reported to be associated with Crohn's disease (CD) susceptibility. We therefore sought to evaluate MEFV as an inflammatory bowel disease (IBD) susceptibility gene.
MEFV colonic mucosal gene expression was significantly increased in experimental colitis mice models (TNBS p |
| doi_str_mv | 10.1371/journal.pone.0007154 |
| format | Article |
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MEFV colonic mucosal gene expression was significantly increased in experimental colitis mice models (TNBS p<0.0003; DSS p<0.006), in biopsies from CD (p<0.02) and severe ulcerative colitis (UC) patients (p<0.008). Comprehensive genetic screening of the MEFV region in the Belgian exploratory sample set (440 CD trios, 137 UC trios, 239 CD cases, 96 UC cases, and 107 healthy controls) identified SNPs located in the MEFV 5' haplotype block that were significantly associated with UC (rs224217; p = 0.003; A allele frequency: 56% cases, 45% controls), while no CD associations were observed. Sequencing and subsequent genotyping of variants located in this associated haplotype block identified three synonymous variants (D102D/rs224225, G138G/rs224224, A165A/rs224223) and one non-synonymous variant (R202Q/rs224222) located in MEFV exon 2 that were significantly associated with UC (rs224222: p = 0.0005; A allele frequency: 32% in cases, 23% in controls). No consistent associations were observed in additional Canadian (256 CD trios, 91 UC trios) and Scottish (495 UC, 370 controls) sample sets. We note that rs224222 showed marginal association (p = 0.012; G allele frequency: 82% in cases, 70% in controls) in the Canadian sample, but with a different risk allele. None of the NLRP3 common variants were associated with UC in the Belgian-Canadian UC samples and no significant interactions were observed between NLRP3 and MEFV that could explain the observed flip-flop of the rs224222 risk allele.
The differences in association levels observed between the sample sets may be a consequence of distinct founder effects or of the relative small sample size of the cohorts evaluated in this study. However, the results suggest that common variants in the MEFV region do not contribute to CD and UC susceptibility.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0007154</identifier><identifier>PMID: 19784369</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Animal models ; Caspase ; Caspase 1 - metabolism ; Caspase-1 ; Child ; Child, Preschool ; Cohort Studies ; Colitis ; Colitis, Ulcerative - genetics ; Colon ; Crohn Disease - genetics ; Crohn's Disease ; Crohns disease ; Cryopyrin ; Cytokines ; Cytoskeletal Proteins - genetics ; Cytoskeletal Proteins - metabolism ; Disease susceptibility ; DNA polymerase ; Enzyme Activation ; Epistasis, Genetic ; Familial Mediterranean fever ; Familial Mediterranean Fever - genetics ; Female ; Fever ; Gastroenterology ; Gastroenterology & hepatology ; Gastroenterology and Hepatology/Inflammatory Bowel Disease ; Gastroentérologie & hépatologie ; Gene expression ; Gene frequency ; Genes ; Genetic aspects ; Genetic diversity ; Genetic Predisposition to Disease ; Genetic research ; Genetic screening ; Genetic testing ; Genetic Variation ; Genetics and Genomics/Complex Traits ; Genetics and Genomics/Gene Expression ; Genetics and Genomics/Genetics of Disease ; Genotyping ; Haplotypes ; Health risks ; Hospitals ; Human health sciences ; Humans ; IL-1β ; Immunology/Innate Immunity ; Inflammasomes ; Inflammation ; Inflammatory bowel disease ; Inflammatory bowel diseases ; Inflammatory Bowel Diseases - genetics ; Interleukin-1beta - metabolism ; Intestine ; Jewish people ; Male ; Medical research ; Medicine ; Middle Aged ; Mucosa ; Mutation ; Pathogenesis ; Periodic disease ; Polymerase chain reaction ; Pyrin ; Pyrin protein ; R&D ; Research & development ; Risk ; Risk factors ; Rodents ; Sciences de la santé humaine ; Single-nucleotide polymorphism ; Thermus aquaticus ; Ulcerative colitis</subject><ispartof>PloS one, 2009-09, Vol.4 (9), p.e7154-e7154</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Villani et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (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>Villani et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c673t-c240a8b9a41a02a3c6afd5210585507b30bb815ced3b920e117db0032c18da0a3</citedby><cites>FETCH-LOGICAL-c673t-c240a8b9a41a02a3c6afd5210585507b30bb815ced3b920e117db0032c18da0a3</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/PMC2745755/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745755/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19784369$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Villani, Alexandra-Chloé</creatorcontrib><creatorcontrib>Lemire, Mathieu</creatorcontrib><creatorcontrib>Louis, Edouard</creatorcontrib><creatorcontrib>Silverberg, Mark S</creatorcontrib><creatorcontrib>Collette, Catherine</creatorcontrib><creatorcontrib>Fortin, Geneviève</creatorcontrib><creatorcontrib>Nimmo, Elaine R</creatorcontrib><creatorcontrib>Renaud, Yannick</creatorcontrib><creatorcontrib>Brunet, Sébastien</creatorcontrib><creatorcontrib>Libioulle, Cécile</creatorcontrib><creatorcontrib>Belaiche, Jacques</creatorcontrib><creatorcontrib>Bitton, Alain</creatorcontrib><creatorcontrib>Gaudet, Daniel</creatorcontrib><creatorcontrib>Cohen, Albert</creatorcontrib><creatorcontrib>Langelier, Diane</creatorcontrib><creatorcontrib>Rioux, John D</creatorcontrib><creatorcontrib>Arnott, Ian D R</creatorcontrib><creatorcontrib>Wild, Gary E</creatorcontrib><creatorcontrib>Rutgeerts, Paul</creatorcontrib><creatorcontrib>Satsangi, Jack</creatorcontrib><creatorcontrib>Vermeire, Séverine</creatorcontrib><creatorcontrib>Hudson, Thomas J</creatorcontrib><creatorcontrib>Franchimont, Denis</creatorcontrib><title>Genetic variation in the familial Mediterranean fever gene (MEFV) and risk for Crohn's disease and ulcerative colitis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has been shown to interact with the gene product of NLRP3, NALP3/cryopyrin, also an important active member of the inflammasome. The NLRP3 region was recently reported to be associated with Crohn's disease (CD) susceptibility. We therefore sought to evaluate MEFV as an inflammatory bowel disease (IBD) susceptibility gene.
MEFV colonic mucosal gene expression was significantly increased in experimental colitis mice models (TNBS p<0.0003; DSS p<0.006), in biopsies from CD (p<0.02) and severe ulcerative colitis (UC) patients (p<0.008). Comprehensive genetic screening of the MEFV region in the Belgian exploratory sample set (440 CD trios, 137 UC trios, 239 CD cases, 96 UC cases, and 107 healthy controls) identified SNPs located in the MEFV 5' haplotype block that were significantly associated with UC (rs224217; p = 0.003; A allele frequency: 56% cases, 45% controls), while no CD associations were observed. Sequencing and subsequent genotyping of variants located in this associated haplotype block identified three synonymous variants (D102D/rs224225, G138G/rs224224, A165A/rs224223) and one non-synonymous variant (R202Q/rs224222) located in MEFV exon 2 that were significantly associated with UC (rs224222: p = 0.0005; A allele frequency: 32% in cases, 23% in controls). No consistent associations were observed in additional Canadian (256 CD trios, 91 UC trios) and Scottish (495 UC, 370 controls) sample sets. We note that rs224222 showed marginal association (p = 0.012; G allele frequency: 82% in cases, 70% in controls) in the Canadian sample, but with a different risk allele. None of the NLRP3 common variants were associated with UC in the Belgian-Canadian UC samples and no significant interactions were observed between NLRP3 and MEFV that could explain the observed flip-flop of the rs224222 risk allele.
The differences in association levels observed between the sample sets may be a consequence of distinct founder effects or of the relative small sample size of the cohorts evaluated in this study. However, the results suggest that common variants in the MEFV region do not contribute to CD and UC susceptibility.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alleles</subject><subject>Animal models</subject><subject>Caspase</subject><subject>Caspase 1 - metabolism</subject><subject>Caspase-1</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cohort Studies</subject><subject>Colitis</subject><subject>Colitis, Ulcerative - genetics</subject><subject>Colon</subject><subject>Crohn Disease - genetics</subject><subject>Crohn's Disease</subject><subject>Crohns disease</subject><subject>Cryopyrin</subject><subject>Cytokines</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>Disease susceptibility</subject><subject>DNA polymerase</subject><subject>Enzyme Activation</subject><subject>Epistasis, Genetic</subject><subject>Familial Mediterranean fever</subject><subject>Familial Mediterranean Fever - genetics</subject><subject>Female</subject><subject>Fever</subject><subject>Gastroenterology</subject><subject>Gastroenterology & hepatology</subject><subject>Gastroenterology and Hepatology/Inflammatory Bowel Disease</subject><subject>Gastroentérologie & hépatologie</subject><subject>Gene expression</subject><subject>Gene frequency</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic research</subject><subject>Genetic screening</subject><subject>Genetic testing</subject><subject>Genetic Variation</subject><subject>Genetics and Genomics/Complex Traits</subject><subject>Genetics and Genomics/Gene Expression</subject><subject>Genetics and Genomics/Genetics of Disease</subject><subject>Genotyping</subject><subject>Haplotypes</subject><subject>Health risks</subject><subject>Hospitals</subject><subject>Human health sciences</subject><subject>Humans</subject><subject>IL-1β</subject><subject>Immunology/Innate Immunity</subject><subject>Inflammasomes</subject><subject>Inflammation</subject><subject>Inflammatory bowel disease</subject><subject>Inflammatory bowel diseases</subject><subject>Inflammatory Bowel Diseases - genetics</subject><subject>Interleukin-1beta - metabolism</subject><subject>Intestine</subject><subject>Jewish people</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Mucosa</subject><subject>Mutation</subject><subject>Pathogenesis</subject><subject>Periodic disease</subject><subject>Polymerase chain reaction</subject><subject>Pyrin</subject><subject>Pyrin protein</subject><subject>R&D</subject><subject>Research & development</subject><subject>Risk</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Sciences de la santé humaine</subject><subject>Single-nucleotide polymorphism</subject><subject>Thermus aquaticus</subject><subject>Ulcerative colitis</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUstuFDEQHCEQCYE_QGCJQ-Cwi5_jmQtSFCUhUiIuwNVqe3o2XrzjjT2zEn-P9wEkCPlgq7uq-uGqqteMzpnQ7OMyTmmAMF_HAeeUUs2UfFIds1bwWc2pePrgfVS9yHlJqRJNXT-vjlirGynq9riarnDA0TuygeRh9HEgfiDjHZIeVj54COQWOz9iSjAgDKTHDSayKCzy_vbi8vsHAkNHks8_SB8TOU_xbjjNpPMZIeMuOQWHqWhvkLgY_Ojzy-pZDyHjq8N9Un27vPh6_nl28-Xq-vzsZuZqLcaZ45JCY1uQDCgH4WroO8UZVY1SVFtBrW2YctgJ23KKjOnOUiq4Y00HFMRJ9Xavuw4xm8PGsmG85ZzXDeMFcb1HdBGWZp38CtJPE8GbXSCmhYFU9hPQdB1lrHXSSuCyocoqKUECaM2c7e1W69Oh2mRX2DkcxgThkejjzODvzCJuDNdSaaWKAN8LBI8LLMWtNxu-I-7eUyjdOGPRbLsvY2jOCun0UDXF-wnzaFY-Owyh_FecstFC0low1hTku3-Q_9_IfI9aQBnaD30svbpyOlx5V8zW-xI_k5o3aksqBLknuBRzTtj_mZhRs7Xq7zJma1VzsGqhvXm4rb-kgzfFL7975p8</recordid><startdate>20090928</startdate><enddate>20090928</enddate><creator>Villani, 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variation in the familial Mediterranean fever gene (MEFV) and risk for Crohn's disease and ulcerative colitis</title><author>Villani, Alexandra-Chloé ; Lemire, Mathieu ; Louis, Edouard ; Silverberg, Mark S ; Collette, Catherine ; Fortin, Geneviève ; Nimmo, Elaine R ; Renaud, Yannick ; Brunet, Sébastien ; Libioulle, Cécile ; Belaiche, Jacques ; Bitton, Alain ; Gaudet, Daniel ; Cohen, Albert ; Langelier, Diane ; Rioux, John D ; Arnott, Ian D R ; Wild, Gary E ; Rutgeerts, Paul ; Satsangi, Jack ; Vermeire, Séverine ; Hudson, Thomas J ; Franchimont, Denis</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c673t-c240a8b9a41a02a3c6afd5210585507b30bb815ced3b920e117db0032c18da0a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alleles</topic><topic>Animal models</topic><topic>Caspase</topic><topic>Caspase 1 - metabolism</topic><topic>Caspase-1</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Cohort Studies</topic><topic>Colitis</topic><topic>Colitis, Ulcerative - genetics</topic><topic>Colon</topic><topic>Crohn Disease - genetics</topic><topic>Crohn's Disease</topic><topic>Crohns disease</topic><topic>Cryopyrin</topic><topic>Cytokines</topic><topic>Cytoskeletal Proteins - genetics</topic><topic>Cytoskeletal Proteins - metabolism</topic><topic>Disease susceptibility</topic><topic>DNA polymerase</topic><topic>Enzyme Activation</topic><topic>Epistasis, Genetic</topic><topic>Familial Mediterranean fever</topic><topic>Familial Mediterranean Fever - genetics</topic><topic>Female</topic><topic>Fever</topic><topic>Gastroenterology</topic><topic>Gastroenterology & hepatology</topic><topic>Gastroenterology and Hepatology/Inflammatory Bowel Disease</topic><topic>Gastroentérologie & hépatologie</topic><topic>Gene 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people</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Middle Aged</topic><topic>Mucosa</topic><topic>Mutation</topic><topic>Pathogenesis</topic><topic>Periodic disease</topic><topic>Polymerase chain reaction</topic><topic>Pyrin</topic><topic>Pyrin protein</topic><topic>R&D</topic><topic>Research & development</topic><topic>Risk</topic><topic>Risk factors</topic><topic>Rodents</topic><topic>Sciences de la santé humaine</topic><topic>Single-nucleotide polymorphism</topic><topic>Thermus aquaticus</topic><topic>Ulcerative colitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Villani, Alexandra-Chloé</creatorcontrib><creatorcontrib>Lemire, Mathieu</creatorcontrib><creatorcontrib>Louis, Edouard</creatorcontrib><creatorcontrib>Silverberg, Mark S</creatorcontrib><creatorcontrib>Collette, Catherine</creatorcontrib><creatorcontrib>Fortin, Geneviève</creatorcontrib><creatorcontrib>Nimmo, Elaine 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(Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest 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Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & 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 & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & 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>Université de Liège - Open Repository and Bibliography (ORBI)</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>Villani, Alexandra-Chloé</au><au>Lemire, Mathieu</au><au>Louis, Edouard</au><au>Silverberg, Mark S</au><au>Collette, Catherine</au><au>Fortin, Geneviève</au><au>Nimmo, Elaine R</au><au>Renaud, Yannick</au><au>Brunet, Sébastien</au><au>Libioulle, Cécile</au><au>Belaiche, Jacques</au><au>Bitton, Alain</au><au>Gaudet, Daniel</au><au>Cohen, Albert</au><au>Langelier, Diane</au><au>Rioux, John D</au><au>Arnott, Ian D R</au><au>Wild, Gary E</au><au>Rutgeerts, Paul</au><au>Satsangi, Jack</au><au>Vermeire, Séverine</au><au>Hudson, Thomas J</au><au>Franchimont, Denis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic variation in the familial Mediterranean fever gene (MEFV) and risk for Crohn's disease and ulcerative colitis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-09-28</date><risdate>2009</risdate><volume>4</volume><issue>9</issue><spage>e7154</spage><epage>e7154</epage><pages>e7154-e7154</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has been shown to interact with the gene product of NLRP3, NALP3/cryopyrin, also an important active member of the inflammasome. The NLRP3 region was recently reported to be associated with Crohn's disease (CD) susceptibility. We therefore sought to evaluate MEFV as an inflammatory bowel disease (IBD) susceptibility gene.
MEFV colonic mucosal gene expression was significantly increased in experimental colitis mice models (TNBS p<0.0003; DSS p<0.006), in biopsies from CD (p<0.02) and severe ulcerative colitis (UC) patients (p<0.008). Comprehensive genetic screening of the MEFV region in the Belgian exploratory sample set (440 CD trios, 137 UC trios, 239 CD cases, 96 UC cases, and 107 healthy controls) identified SNPs located in the MEFV 5' haplotype block that were significantly associated with UC (rs224217; p = 0.003; A allele frequency: 56% cases, 45% controls), while no CD associations were observed. Sequencing and subsequent genotyping of variants located in this associated haplotype block identified three synonymous variants (D102D/rs224225, G138G/rs224224, A165A/rs224223) and one non-synonymous variant (R202Q/rs224222) located in MEFV exon 2 that were significantly associated with UC (rs224222: p = 0.0005; A allele frequency: 32% in cases, 23% in controls). No consistent associations were observed in additional Canadian (256 CD trios, 91 UC trios) and Scottish (495 UC, 370 controls) sample sets. We note that rs224222 showed marginal association (p = 0.012; G allele frequency: 82% in cases, 70% in controls) in the Canadian sample, but with a different risk allele. None of the NLRP3 common variants were associated with UC in the Belgian-Canadian UC samples and no significant interactions were observed between NLRP3 and MEFV that could explain the observed flip-flop of the rs224222 risk allele.
The differences in association levels observed between the sample sets may be a consequence of distinct founder effects or of the relative small sample size of the cohorts evaluated in this study. However, the results suggest that common variants in the MEFV region do not contribute to CD and UC susceptibility.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19784369</pmid><doi>10.1371/journal.pone.0007154</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2009-09, Vol.4 (9), p.e7154-e7154 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1292226812 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adolescent Adult Aged Aged, 80 and over Alleles Animal models Caspase Caspase 1 - metabolism Caspase-1 Child Child, Preschool Cohort Studies Colitis Colitis, Ulcerative - genetics Colon Crohn Disease - genetics Crohn's Disease Crohns disease Cryopyrin Cytokines Cytoskeletal Proteins - genetics Cytoskeletal Proteins - metabolism Disease susceptibility DNA polymerase Enzyme Activation Epistasis, Genetic Familial Mediterranean fever Familial Mediterranean Fever - genetics Female Fever Gastroenterology Gastroenterology & hepatology Gastroenterology and Hepatology/Inflammatory Bowel Disease Gastroentérologie & hépatologie Gene expression Gene frequency Genes Genetic aspects Genetic diversity Genetic Predisposition to Disease Genetic research Genetic screening Genetic testing Genetic Variation Genetics and Genomics/Complex Traits Genetics and Genomics/Gene Expression Genetics and Genomics/Genetics of Disease Genotyping Haplotypes Health risks Hospitals Human health sciences Humans IL-1β Immunology/Innate Immunity Inflammasomes Inflammation Inflammatory bowel disease Inflammatory bowel diseases Inflammatory Bowel Diseases - genetics Interleukin-1beta - metabolism Intestine Jewish people Male Medical research Medicine Middle Aged Mucosa Mutation Pathogenesis Periodic disease Polymerase chain reaction Pyrin Pyrin protein R&D Research & development Risk Risk factors Rodents Sciences de la santé humaine Single-nucleotide polymorphism Thermus aquaticus Ulcerative colitis |
| title | Genetic variation in the familial Mediterranean fever gene (MEFV) and risk for Crohn's disease and ulcerative colitis |
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