Genetic Susceptibility to Postdiarrheal Hemolytic-Uremic Syndrome After Shiga Toxin-Producing Escherichia coli Infection: A Centers for Disease Control and Prevention FoodNet Study
Postdiarrheal hemolytic-uremic syndrome (D+HUS) following Shiga toxin-producing Escherichia coli (STEC) infection is a serious condition lacking specific treatment. Host immune dysregulation and genetic susceptibility to complement hyperactivation are implicated in non-STEC-related HUS. However, gen...
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| Veröffentlicht in: | The Journal of infectious diseases 2018-03, Vol.217 (6), p.1000-1010 |
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| creator | Kallianpur, Asha R Bradford, Yuki Mody, Rajal K Garman, Katie N Comstock, Nicole Lathrop, Sarah L Lyons, Carol Saupe, Amy Wymore, Katie Canter, Jeffrey A Olson, Lana M Palmer, Amanda Jones, Timothy F |
| description | Postdiarrheal hemolytic-uremic syndrome (D+HUS) following Shiga toxin-producing Escherichia coli (STEC) infection is a serious condition lacking specific treatment. Host immune dysregulation and genetic susceptibility to complement hyperactivation are implicated in non-STEC-related HUS. However, genetic susceptibility to D+HUS remains largely uncharacterized.
Patients with culture-confirmed STEC diarrhea, identified through the Centers for Disease Control and Prevention FoodNet surveillance system (2007-2012), were serotyped and classified by laboratory and/or clinical criteria as having suspected, probable, or confirmed D+HUS or as controls and underwent genotyping at 200 loci linked to nondiarrheal HUS or similar pathologies. Genetic associations with D+HUS were explored by multivariable regression, with adjustment for known risk factors.
Of 641 enrollees with STEC O157:H7, 80 had suspected D+HUS (41 with probable and 32 with confirmed D+HUS). Twelve genes related to cytokine signaling, complement pathways, platelet function, pathogen recognition, iron transport, and endothelial function were associated with D+HUS in multivariable-adjusted analyses (P ≤ .05). Of 12 significant single-nucleotide polymorphisms (SNPs), 5 were associated with all levels of D+HUS (intergenic SNP rs10874639, TFRC rs3804141, EDN1 rs5370, GP1BA rs121908064, and B2M rs16966334), and 7 SNPs (6 non-complement related) were associated with confirmed D+HUS (all P < .05).
Polymorphisms in many non-complement-related genes may contribute to D+HUS susceptibility. These results require replication, but they suggest novel therapeutic targets in patients with D+HUS. |
| doi_str_mv | 10.1093/infdis/jix633 |
| format | Article |
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Patients with culture-confirmed STEC diarrhea, identified through the Centers for Disease Control and Prevention FoodNet surveillance system (2007-2012), were serotyped and classified by laboratory and/or clinical criteria as having suspected, probable, or confirmed D+HUS or as controls and underwent genotyping at 200 loci linked to nondiarrheal HUS or similar pathologies. Genetic associations with D+HUS were explored by multivariable regression, with adjustment for known risk factors.
Of 641 enrollees with STEC O157:H7, 80 had suspected D+HUS (41 with probable and 32 with confirmed D+HUS). Twelve genes related to cytokine signaling, complement pathways, platelet function, pathogen recognition, iron transport, and endothelial function were associated with D+HUS in multivariable-adjusted analyses (P ≤ .05). Of 12 significant single-nucleotide polymorphisms (SNPs), 5 were associated with all levels of D+HUS (intergenic SNP rs10874639, TFRC rs3804141, EDN1 rs5370, GP1BA rs121908064, and B2M rs16966334), and 7 SNPs (6 non-complement related) were associated with confirmed D+HUS (all P < .05).
Polymorphisms in many non-complement-related genes may contribute to D+HUS susceptibility. These results require replication, but they suggest novel therapeutic targets in patients with D+HUS.</description><identifier>ISSN: 0022-1899</identifier><identifier>ISSN: 1537-6613</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jix633</identifier><identifier>PMID: 29216383</identifier><language>eng</language><publisher>United States</publisher><subject>Adolescent ; Centers for Disease Control and Prevention, U.S ; Child ; Child, Preschool ; Diarrhea - complications ; Diarrhea - microbiology ; Escherichia coli Infections - complications ; Escherichia coli Infections - microbiology ; Female ; Genetic Predisposition to Disease ; Hemolytic-Uremic Syndrome - genetics ; Hemolytic-Uremic Syndrome - pathology ; Humans ; Male ; Risk Factors ; Shiga-Toxigenic Escherichia coli - pathogenicity ; United States</subject><ispartof>The Journal of infectious diseases, 2018-03, Vol.217 (6), p.1000-1010</ispartof><rights>The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c388t-5f121fcad4de606c234d7b453c1610edb57425f2a8bd708eb93311b34e7d8843</citedby><cites>FETCH-LOGICAL-c388t-5f121fcad4de606c234d7b453c1610edb57425f2a8bd708eb93311b34e7d8843</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29216383$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kallianpur, Asha R</creatorcontrib><creatorcontrib>Bradford, Yuki</creatorcontrib><creatorcontrib>Mody, Rajal K</creatorcontrib><creatorcontrib>Garman, Katie N</creatorcontrib><creatorcontrib>Comstock, Nicole</creatorcontrib><creatorcontrib>Lathrop, Sarah L</creatorcontrib><creatorcontrib>Lyons, Carol</creatorcontrib><creatorcontrib>Saupe, Amy</creatorcontrib><creatorcontrib>Wymore, Katie</creatorcontrib><creatorcontrib>Canter, Jeffrey A</creatorcontrib><creatorcontrib>Olson, Lana M</creatorcontrib><creatorcontrib>Palmer, Amanda</creatorcontrib><creatorcontrib>Jones, Timothy F</creatorcontrib><title>Genetic Susceptibility to Postdiarrheal Hemolytic-Uremic Syndrome After Shiga Toxin-Producing Escherichia coli Infection: A Centers for Disease Control and Prevention FoodNet Study</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Postdiarrheal hemolytic-uremic syndrome (D+HUS) following Shiga toxin-producing Escherichia coli (STEC) infection is a serious condition lacking specific treatment. Host immune dysregulation and genetic susceptibility to complement hyperactivation are implicated in non-STEC-related HUS. However, genetic susceptibility to D+HUS remains largely uncharacterized.
Patients with culture-confirmed STEC diarrhea, identified through the Centers for Disease Control and Prevention FoodNet surveillance system (2007-2012), were serotyped and classified by laboratory and/or clinical criteria as having suspected, probable, or confirmed D+HUS or as controls and underwent genotyping at 200 loci linked to nondiarrheal HUS or similar pathologies. Genetic associations with D+HUS were explored by multivariable regression, with adjustment for known risk factors.
Of 641 enrollees with STEC O157:H7, 80 had suspected D+HUS (41 with probable and 32 with confirmed D+HUS). Twelve genes related to cytokine signaling, complement pathways, platelet function, pathogen recognition, iron transport, and endothelial function were associated with D+HUS in multivariable-adjusted analyses (P ≤ .05). Of 12 significant single-nucleotide polymorphisms (SNPs), 5 were associated with all levels of D+HUS (intergenic SNP rs10874639, TFRC rs3804141, EDN1 rs5370, GP1BA rs121908064, and B2M rs16966334), and 7 SNPs (6 non-complement related) were associated with confirmed D+HUS (all P < .05).
Polymorphisms in many non-complement-related genes may contribute to D+HUS susceptibility. These results require replication, but they suggest novel therapeutic targets in patients with D+HUS.</description><subject>Adolescent</subject><subject>Centers for Disease Control and Prevention, U.S</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Diarrhea - complications</subject><subject>Diarrhea - microbiology</subject><subject>Escherichia coli Infections - complications</subject><subject>Escherichia coli Infections - microbiology</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Hemolytic-Uremic Syndrome - genetics</subject><subject>Hemolytic-Uremic Syndrome - pathology</subject><subject>Humans</subject><subject>Male</subject><subject>Risk Factors</subject><subject>Shiga-Toxigenic Escherichia coli - pathogenicity</subject><subject>United States</subject><issn>0022-1899</issn><issn>1537-6613</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkctu2zAQRYmgReOmXWZbcNmNGlLUs5vCcJ5A0BqwuyYocmRNIJEuSQXRf-UDI8Np0G5mFnPmzsVcQs45-8ZZLS7QtgbDxQM-FUKckAXPRZkUBRfvyIKxNE14Vden5GMID4yxTBTlB3Ka1ikvRCUW5PkGLETUdDMGDfuIDfYYJxodXbsQDSrvO1A9vYXB9dNMJr89DIeFyRrvBqDLNoKnmw53im7dE9pk7Z0ZNdodvQq6A4-6Q0W165He2RZ0RGe_0yVdgZ1XA22dp5cYQAWgK2ejdz1V1tC1h8cZmWl67Zz5CZFu4mimT-R9q_oAn1_7GdleX21Xt8n9r5u71fI-0aKqYpK3POWtViYzULBCpyIzZZPlQvOCMzBNXmZp3qaqakzJKmhqIThvRAalqapMnJEfR9n92Axg9GzFq17uPQ7KT9IplP9PLHZy5x4l54JXeSpmha-vCt79GSFEOeD85r5XFtwYJK_LnB1KPqPJEdXeheChfbvDmTwkLY9Jy2PSM__lX3Nv9N9oxQss86vq</recordid><startdate>20180305</startdate><enddate>20180305</enddate><creator>Kallianpur, Asha R</creator><creator>Bradford, Yuki</creator><creator>Mody, Rajal K</creator><creator>Garman, Katie N</creator><creator>Comstock, Nicole</creator><creator>Lathrop, Sarah L</creator><creator>Lyons, Carol</creator><creator>Saupe, Amy</creator><creator>Wymore, Katie</creator><creator>Canter, Jeffrey A</creator><creator>Olson, Lana M</creator><creator>Palmer, Amanda</creator><creator>Jones, Timothy F</creator><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>20180305</creationdate><title>Genetic Susceptibility to Postdiarrheal Hemolytic-Uremic Syndrome After Shiga Toxin-Producing Escherichia coli Infection: A Centers for Disease Control and Prevention FoodNet Study</title><author>Kallianpur, Asha R ; Bradford, Yuki ; Mody, Rajal K ; Garman, Katie N ; Comstock, Nicole ; Lathrop, Sarah L ; Lyons, Carol ; Saupe, Amy ; Wymore, Katie ; Canter, Jeffrey A ; Olson, Lana M ; Palmer, Amanda ; Jones, Timothy F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c388t-5f121fcad4de606c234d7b453c1610edb57425f2a8bd708eb93311b34e7d8843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adolescent</topic><topic>Centers for Disease Control and Prevention, U.S</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Diarrhea - complications</topic><topic>Diarrhea - microbiology</topic><topic>Escherichia coli Infections - complications</topic><topic>Escherichia coli Infections - microbiology</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Hemolytic-Uremic Syndrome - genetics</topic><topic>Hemolytic-Uremic Syndrome - pathology</topic><topic>Humans</topic><topic>Male</topic><topic>Risk Factors</topic><topic>Shiga-Toxigenic Escherichia coli - pathogenicity</topic><topic>United States</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kallianpur, Asha R</creatorcontrib><creatorcontrib>Bradford, Yuki</creatorcontrib><creatorcontrib>Mody, Rajal K</creatorcontrib><creatorcontrib>Garman, Katie N</creatorcontrib><creatorcontrib>Comstock, Nicole</creatorcontrib><creatorcontrib>Lathrop, Sarah L</creatorcontrib><creatorcontrib>Lyons, Carol</creatorcontrib><creatorcontrib>Saupe, Amy</creatorcontrib><creatorcontrib>Wymore, Katie</creatorcontrib><creatorcontrib>Canter, Jeffrey A</creatorcontrib><creatorcontrib>Olson, Lana M</creatorcontrib><creatorcontrib>Palmer, Amanda</creatorcontrib><creatorcontrib>Jones, Timothy F</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>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kallianpur, Asha R</au><au>Bradford, Yuki</au><au>Mody, Rajal K</au><au>Garman, Katie N</au><au>Comstock, Nicole</au><au>Lathrop, Sarah L</au><au>Lyons, Carol</au><au>Saupe, Amy</au><au>Wymore, Katie</au><au>Canter, Jeffrey A</au><au>Olson, Lana M</au><au>Palmer, Amanda</au><au>Jones, Timothy F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Susceptibility to Postdiarrheal Hemolytic-Uremic Syndrome After Shiga Toxin-Producing Escherichia coli Infection: A Centers for Disease Control and Prevention FoodNet Study</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2018-03-05</date><risdate>2018</risdate><volume>217</volume><issue>6</issue><spage>1000</spage><epage>1010</epage><pages>1000-1010</pages><issn>0022-1899</issn><issn>1537-6613</issn><eissn>1537-6613</eissn><abstract>Postdiarrheal hemolytic-uremic syndrome (D+HUS) following Shiga toxin-producing Escherichia coli (STEC) infection is a serious condition lacking specific treatment. Host immune dysregulation and genetic susceptibility to complement hyperactivation are implicated in non-STEC-related HUS. However, genetic susceptibility to D+HUS remains largely uncharacterized.
Patients with culture-confirmed STEC diarrhea, identified through the Centers for Disease Control and Prevention FoodNet surveillance system (2007-2012), were serotyped and classified by laboratory and/or clinical criteria as having suspected, probable, or confirmed D+HUS or as controls and underwent genotyping at 200 loci linked to nondiarrheal HUS or similar pathologies. Genetic associations with D+HUS were explored by multivariable regression, with adjustment for known risk factors.
Of 641 enrollees with STEC O157:H7, 80 had suspected D+HUS (41 with probable and 32 with confirmed D+HUS). Twelve genes related to cytokine signaling, complement pathways, platelet function, pathogen recognition, iron transport, and endothelial function were associated with D+HUS in multivariable-adjusted analyses (P ≤ .05). Of 12 significant single-nucleotide polymorphisms (SNPs), 5 were associated with all levels of D+HUS (intergenic SNP rs10874639, TFRC rs3804141, EDN1 rs5370, GP1BA rs121908064, and B2M rs16966334), and 7 SNPs (6 non-complement related) were associated with confirmed D+HUS (all P < .05).
Polymorphisms in many non-complement-related genes may contribute to D+HUS susceptibility. These results require replication, but they suggest novel therapeutic targets in patients with D+HUS.</abstract><cop>United States</cop><pmid>29216383</pmid><doi>10.1093/infdis/jix633</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Centers for Disease Control and Prevention, U.S Child Child, Preschool Diarrhea - complications Diarrhea - microbiology Escherichia coli Infections - complications Escherichia coli Infections - microbiology Female Genetic Predisposition to Disease Hemolytic-Uremic Syndrome - genetics Hemolytic-Uremic Syndrome - pathology Humans Male Risk Factors Shiga-Toxigenic Escherichia coli - pathogenicity United States |
| title | Genetic Susceptibility to Postdiarrheal Hemolytic-Uremic Syndrome After Shiga Toxin-Producing Escherichia coli Infection: A Centers for Disease Control and Prevention FoodNet Study |
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