Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease
Transplantation and pregnancy, in which two diploid genomes reside in one body, can each lead to diseases in which immune cells from one individual target antigens encoded in the other's genome. One such disease, graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HS...
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| Veröffentlicht in: | Nature genetics 2009-12, Vol.41 (12), p.1341-1344 |
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| creator | McCarroll, Steven A Bradner, James E Turpeinen, Hannu Volin, Liisa Martin, Paul J Chilewski, Shannon D Antin, Joseph H Lee, Stephanie J Ruutu, Tapani Storer, Barry Warren, Edus H Zhang, Bo Zhao, Lue Ping Ginsburg, David Soiffer, Robert J Partanen, Jukka Hansen, John A Ritz, Jerome Palotie, Aarno Altshuler, David |
| description | Transplantation and pregnancy, in which two diploid genomes reside in one body, can each lead to diseases in which immune cells from one individual target antigens encoded in the other's genome. One such disease, graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT, or bone marrow transplant), is common even after transplants between HLA-identical siblings, indicating that cryptic histocompatibility loci exist outside the HLA locus. The immune system of an individual whose genome is homozygous for a gene deletion could recognize epitopes encoded by that gene as alloantigens. Analyzing common gene deletions in three HSCT cohorts (1,345 HLA-identical sibling donor-recipient pairs), we found that risk of acute GVHD was greater (odds ratio (OR) = 2.5; 95% confidence interval (CI) 1.4-4.6) when donor and recipient were mismatched for homozygous deletion of UGT2B17, a gene expressed in GVHD-affected tissues and giving rise to multiple histocompatibility antigens. Human genome structural variation merits investigation as a potential mechanism in diseases of alloimmunity. |
| doi_str_mv | 10.1038/ng.490 |
| format | Article |
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One such disease, graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT, or bone marrow transplant), is common even after transplants between HLA-identical siblings, indicating that cryptic histocompatibility loci exist outside the HLA locus. The immune system of an individual whose genome is homozygous for a gene deletion could recognize epitopes encoded by that gene as alloantigens. Analyzing common gene deletions in three HSCT cohorts (1,345 HLA-identical sibling donor-recipient pairs), we found that risk of acute GVHD was greater (odds ratio (OR) = 2.5; 95% confidence interval (CI) 1.4-4.6) when donor and recipient were mismatched for homozygous deletion of UGT2B17, a gene expressed in GVHD-affected tissues and giving rise to multiple histocompatibility antigens. Human genome structural variation merits investigation as a potential mechanism in diseases of alloimmunity.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng.490</identifier><identifier>PMID: 19935662</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Amino acids ; Animal Genetics and Genomics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Bone marrow ; Bone Marrow Transplantation ; Cancer ; Cancer Research ; Cohort Studies ; Complications and side effects ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Deletion ; Gene Function ; Gene mutations ; Genes ; Genetic aspects ; Genetics ; Genetics of eukaryotes. Biological and molecular evolution ; Genome, Human ; Genotype & phenotype ; Glucuronosyltransferase - genetics ; Graft versus host reaction ; Graft vs Host Disease - genetics ; Graft vs Host Disease - immunology ; Health aspects ; Hematopoietic Stem Cell Transplantation ; Hematopoietic stem cells ; HLA Antigens - genetics ; Hospitals ; Human Genetics ; Humans ; Immune system ; letter ; Life sciences ; Lymphocytes ; Male ; Medical research ; Minor Histocompatibility Antigens ; Patients ; Polymorphism, Genetic ; Risk factors ; Stem cells ; Transplantation ; Transplants & implants</subject><ispartof>Nature genetics, 2009-12, Vol.41 (12), p.1341-1344</ispartof><rights>Springer Nature America, Inc. 2009</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2009 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Dec 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c610t-c25f9a879961b94fc1e227ec4840a565fc8be3f5651441160bd44926f996fd9c3</citedby><cites>FETCH-LOGICAL-c610t-c25f9a879961b94fc1e227ec4840a565fc8be3f5651441160bd44926f996fd9c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ng.490$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ng.490$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,2726,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22194608$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19935662$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McCarroll, Steven A</creatorcontrib><creatorcontrib>Bradner, James E</creatorcontrib><creatorcontrib>Turpeinen, Hannu</creatorcontrib><creatorcontrib>Volin, Liisa</creatorcontrib><creatorcontrib>Martin, Paul J</creatorcontrib><creatorcontrib>Chilewski, Shannon D</creatorcontrib><creatorcontrib>Antin, Joseph H</creatorcontrib><creatorcontrib>Lee, Stephanie J</creatorcontrib><creatorcontrib>Ruutu, Tapani</creatorcontrib><creatorcontrib>Storer, Barry</creatorcontrib><creatorcontrib>Warren, Edus H</creatorcontrib><creatorcontrib>Zhang, Bo</creatorcontrib><creatorcontrib>Zhao, Lue Ping</creatorcontrib><creatorcontrib>Ginsburg, David</creatorcontrib><creatorcontrib>Soiffer, Robert J</creatorcontrib><creatorcontrib>Partanen, Jukka</creatorcontrib><creatorcontrib>Hansen, John A</creatorcontrib><creatorcontrib>Ritz, Jerome</creatorcontrib><creatorcontrib>Palotie, Aarno</creatorcontrib><creatorcontrib>Altshuler, David</creatorcontrib><title>Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Transplantation and pregnancy, in which two diploid genomes reside in one body, can each lead to diseases in which immune cells from one individual target antigens encoded in the other's genome. One such disease, graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT, or bone marrow transplant), is common even after transplants between HLA-identical siblings, indicating that cryptic histocompatibility loci exist outside the HLA locus. The immune system of an individual whose genome is homozygous for a gene deletion could recognize epitopes encoded by that gene as alloantigens. Analyzing common gene deletions in three HSCT cohorts (1,345 HLA-identical sibling donor-recipient pairs), we found that risk of acute GVHD was greater (odds ratio (OR) = 2.5; 95% confidence interval (CI) 1.4-4.6) when donor and recipient were mismatched for homozygous deletion of UGT2B17, a gene expressed in GVHD-affected tissues and giving rise to multiple histocompatibility antigens. Human genome structural variation merits investigation as a potential mechanism in diseases of alloimmunity.</description><subject>Agriculture</subject><subject>Amino acids</subject><subject>Animal Genetics and Genomics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bone marrow</subject><subject>Bone Marrow Transplantation</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Cohort Studies</subject><subject>Complications and side effects</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Deletion</subject><subject>Gene Function</subject><subject>Gene mutations</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetics</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genome, Human</subject><subject>Genotype & phenotype</subject><subject>Glucuronosyltransferase - genetics</subject><subject>Graft versus host reaction</subject><subject>Graft vs Host Disease - genetics</subject><subject>Graft vs Host Disease - immunology</subject><subject>Health aspects</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Hematopoietic stem cells</subject><subject>HLA Antigens - genetics</subject><subject>Hospitals</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immune system</subject><subject>letter</subject><subject>Life sciences</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Medical research</subject><subject>Minor Histocompatibility Antigens</subject><subject>Patients</subject><subject>Polymorphism, Genetic</subject><subject>Risk factors</subject><subject>Stem cells</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkluL1TAQx4so7kX9BCJFUfGhxyRN0-ZFWNbbwsKCtych5KSTnixtUpN22f32ztLDWQ_6IHnIZX7zn8mfybInlKwoKZu3vltxSe5lh7TioqA1be7jmQhacFKKg-wopUtCKOekeZgdUCnLSgh2mP18H3yIRQTjRgd-ygeXBj2ZTW5DzE0YhuDzDjzkLfQwObyNob8ZQhw3SKbcYThqOxVXENOcik1IU966BDrBo-yB1X2Cx9v9OPv-8cO308_F-cWns9OT88IISqbCsMpK3dRSCrqW3BoKjNVgeMOJrkRlTbOG0uIJ-6dUkHXLuWTCYoJtpSmPs3eL7jivB2gN_iPqXo3RDTreqKCd2o94t1FduFKsIbzmFQo83wrE8GuGNKnLMEePPSvGGNat2S30YoE63YNy3gbUMuiXUSeMlkLSuqJIrf5B4WphcCZ4sA7f9xLe7CUgM8H11Ok5JXX29cv_sxc_9tlXC2tiSCmC3flBibqdGeU7hTOD4LM_3bvDtkOCwMstoJPRvY3aG5d2HGNUckEa5F4vXMKQ7yDeufhXyacL6fU0R9hJbcO_Af8j3o0</recordid><startdate>20091201</startdate><enddate>20091201</enddate><creator>McCarroll, Steven A</creator><creator>Bradner, James E</creator><creator>Turpeinen, Hannu</creator><creator>Volin, Liisa</creator><creator>Martin, Paul J</creator><creator>Chilewski, Shannon D</creator><creator>Antin, Joseph H</creator><creator>Lee, Stephanie J</creator><creator>Ruutu, Tapani</creator><creator>Storer, Barry</creator><creator>Warren, Edus H</creator><creator>Zhang, Bo</creator><creator>Zhao, Lue Ping</creator><creator>Ginsburg, David</creator><creator>Soiffer, Robert J</creator><creator>Partanen, Jukka</creator><creator>Hansen, John A</creator><creator>Ritz, Jerome</creator><creator>Palotie, Aarno</creator><creator>Altshuler, David</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>IQODW</scope><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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20091201</creationdate><title>Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease</title><author>McCarroll, Steven A ; Bradner, James E ; Turpeinen, Hannu ; Volin, Liisa ; Martin, Paul J ; Chilewski, Shannon D ; Antin, Joseph H ; Lee, Stephanie J ; Ruutu, Tapani ; Storer, Barry ; Warren, Edus H ; Zhang, Bo ; Zhao, Lue Ping ; Ginsburg, David ; Soiffer, Robert J ; Partanen, Jukka ; Hansen, John A ; Ritz, Jerome ; Palotie, Aarno ; Altshuler, David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c610t-c25f9a879961b94fc1e227ec4840a565fc8be3f5651441160bd44926f996fd9c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Agriculture</topic><topic>Amino acids</topic><topic>Animal Genetics and Genomics</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bone marrow</topic><topic>Bone Marrow Transplantation</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Cohort Studies</topic><topic>Complications and side effects</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Deletion</topic><topic>Gene Function</topic><topic>Gene mutations</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetics</topic><topic>Genetics of eukaryotes. 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| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2009-12, Vol.41 (12), p.1341-1344 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2804745 |
| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | Agriculture Amino acids Animal Genetics and Genomics Biological and medical sciences Biomedical and Life Sciences Biomedicine Bone marrow Bone Marrow Transplantation Cancer Cancer Research Cohort Studies Complications and side effects Female Fundamental and applied biological sciences. Psychology Gene Deletion Gene Function Gene mutations Genes Genetic aspects Genetics Genetics of eukaryotes. Biological and molecular evolution Genome, Human Genotype & phenotype Glucuronosyltransferase - genetics Graft versus host reaction Graft vs Host Disease - genetics Graft vs Host Disease - immunology Health aspects Hematopoietic Stem Cell Transplantation Hematopoietic stem cells HLA Antigens - genetics Hospitals Human Genetics Humans Immune system letter Life sciences Lymphocytes Male Medical research Minor Histocompatibility Antigens Patients Polymorphism, Genetic Risk factors Stem cells Transplantation Transplants & implants |
| title | Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T07%3A04%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Donor-recipient%20mismatch%20for%20common%20gene%20deletion%20polymorphisms%20in%20graft-versus-host%20disease&rft.jtitle=Nature%20genetics&rft.au=McCarroll,%20Steven%20A&rft.date=2009-12-01&rft.volume=41&rft.issue=12&rft.spage=1341&rft.epage=1344&rft.pages=1341-1344&rft.issn=1061-4036&rft.eissn=1546-1718&rft.coden=NGENEC&rft_id=info:doi/10.1038/ng.490&rft_dat=%3Cgale_pubme%3EA213691751%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222651725&rft_id=info:pmid/19935662&rft_galeid=A213691751&rfr_iscdi=true |