Toll-like receptor genetic variations in bone marrow transplantation
The Toll-like receptor family mediates the innate immune system through recognizing the molecular patterns of microorganisms and self-components and leading the synthesis of the inflammatory mediators. We retrospectively examined whether or not genetic variations in toll-like receptor 1 (rs5743551,...
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| Veröffentlicht in: | Oncotarget 2017-07, Vol.8 (28), p.45670-45686 |
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| creator | Uchino, Kaori Mizuno, Shohei Sato-Otsubo, Aiko Nannya, Yasuhito Mizutani, Motonori Horio, Tomohiro Hanamura, Ichiro Espinoza, J Luis Onizuka, Makoto Kashiwase, Koichi Morishima, Yasuo Fukuda, Takahiro Kodera, Yoshihisa Doki, Noriko Miyamura, Koichi Mori, Takehiko Ogawa, Seishi Takami, Akiyoshi |
| description | The Toll-like receptor family mediates the innate immune system through recognizing the molecular patterns of microorganisms and self-components and leading the synthesis of the inflammatory mediators. We retrospectively examined whether or not genetic variations in toll-like receptor 1 (rs5743551, -7202GQ>A), toll-like receptor 2 (rs7656411, 22215G>T), and toll-like receptor 4 (rs11536889, +3725G>C) affected transplant outcomes in a cohort of 365 patients who underwent unrelated HLA-matched bone marrow transplantation (for hematologic malignancies through the Japan Marrow Donor Program. Only donor toll-like receptor 4 variation significantly improved the survival outcomes. A multivariate analysis showed that the donor toll-like receptor 4 +3725G/G genotype was significantly associated with a better 5-year progression-free survival and a lower 5-year transplant-related mortality than other variations. Furthermore, the donor toll-like receptor 4 +3725G/G genotype was associated with a significantly lower incidence of fatal infections than other variations. The validation study of 502 patients confirmed that the donor toll-like receptor 4 +3725G/G genotype was associated with better survival outcomes. Toll-like receptor4 genotyping in transplant donors may therefore be a useful tool for optimizing donor selection and evaluating pretransplantation risks. |
| doi_str_mv | 10.18632/oncotarget.17315 |
| format | Article |
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We retrospectively examined whether or not genetic variations in toll-like receptor 1 (rs5743551, -7202GQ>A), toll-like receptor 2 (rs7656411, 22215G>T), and toll-like receptor 4 (rs11536889, +3725G>C) affected transplant outcomes in a cohort of 365 patients who underwent unrelated HLA-matched bone marrow transplantation (for hematologic malignancies through the Japan Marrow Donor Program. Only donor toll-like receptor 4 variation significantly improved the survival outcomes. A multivariate analysis showed that the donor toll-like receptor 4 +3725G/G genotype was significantly associated with a better 5-year progression-free survival and a lower 5-year transplant-related mortality than other variations. Furthermore, the donor toll-like receptor 4 +3725G/G genotype was associated with a significantly lower incidence of fatal infections than other variations. The validation study of 502 patients confirmed that the donor toll-like receptor 4 +3725G/G genotype was associated with better survival outcomes. Toll-like receptor4 genotyping in transplant donors may therefore be a useful tool for optimizing donor selection and evaluating pretransplantation risks.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.17315</identifier><identifier>PMID: 28484092</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Adolescent ; Adult ; Aged ; Alleles ; Bone Marrow Transplantation - adverse effects ; Bone Marrow Transplantation - methods ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genetic Variation ; Genotype ; Graft vs Host Disease - diagnosis ; Graft vs Host Disease - etiology ; Hematologic Neoplasms - genetics ; Hematologic Neoplasms - therapy ; Hematopoietic Stem Cell Transplantation ; Histocompatibility Testing ; HLA Antigens - genetics ; HLA Antigens - immunology ; Humans ; Infant ; Infection - etiology ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Research Paper ; Toll-Like Receptors - genetics ; Transplantation, Homologous ; Treatment Outcome ; Unrelated Donors ; Young Adult</subject><ispartof>Oncotarget, 2017-07, Vol.8 (28), p.45670-45686</ispartof><rights>Copyright: © 2017 Uchino et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-72ee9c51fd511f01ea9342489f0fe37f37b84564a019edcb417b1b120f9df66e3</citedby><cites>FETCH-LOGICAL-c422t-72ee9c51fd511f01ea9342489f0fe37f37b84564a019edcb417b1b120f9df66e3</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/PMC5542217/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542217/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28484092$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Uchino, Kaori</creatorcontrib><creatorcontrib>Mizuno, Shohei</creatorcontrib><creatorcontrib>Sato-Otsubo, Aiko</creatorcontrib><creatorcontrib>Nannya, Yasuhito</creatorcontrib><creatorcontrib>Mizutani, Motonori</creatorcontrib><creatorcontrib>Horio, Tomohiro</creatorcontrib><creatorcontrib>Hanamura, Ichiro</creatorcontrib><creatorcontrib>Espinoza, J Luis</creatorcontrib><creatorcontrib>Onizuka, Makoto</creatorcontrib><creatorcontrib>Kashiwase, Koichi</creatorcontrib><creatorcontrib>Morishima, Yasuo</creatorcontrib><creatorcontrib>Fukuda, Takahiro</creatorcontrib><creatorcontrib>Kodera, Yoshihisa</creatorcontrib><creatorcontrib>Doki, Noriko</creatorcontrib><creatorcontrib>Miyamura, Koichi</creatorcontrib><creatorcontrib>Mori, Takehiko</creatorcontrib><creatorcontrib>Ogawa, Seishi</creatorcontrib><creatorcontrib>Takami, Akiyoshi</creatorcontrib><title>Toll-like receptor genetic variations in bone marrow transplantation</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>The Toll-like receptor family mediates the innate immune system through recognizing the molecular patterns of microorganisms and self-components and leading the synthesis of the inflammatory mediators. We retrospectively examined whether or not genetic variations in toll-like receptor 1 (rs5743551, -7202GQ>A), toll-like receptor 2 (rs7656411, 22215G>T), and toll-like receptor 4 (rs11536889, +3725G>C) affected transplant outcomes in a cohort of 365 patients who underwent unrelated HLA-matched bone marrow transplantation (for hematologic malignancies through the Japan Marrow Donor Program. Only donor toll-like receptor 4 variation significantly improved the survival outcomes. A multivariate analysis showed that the donor toll-like receptor 4 +3725G/G genotype was significantly associated with a better 5-year progression-free survival and a lower 5-year transplant-related mortality than other variations. Furthermore, the donor toll-like receptor 4 +3725G/G genotype was associated with a significantly lower incidence of fatal infections than other variations. The validation study of 502 patients confirmed that the donor toll-like receptor 4 +3725G/G genotype was associated with better survival outcomes. Toll-like receptor4 genotyping in transplant donors may therefore be a useful tool for optimizing donor selection and evaluating pretransplantation risks.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Alleles</subject><subject>Bone Marrow Transplantation - adverse effects</subject><subject>Bone Marrow Transplantation - methods</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genetic Variation</subject><subject>Genotype</subject><subject>Graft vs Host Disease - diagnosis</subject><subject>Graft vs Host Disease - etiology</subject><subject>Hematologic Neoplasms - genetics</subject><subject>Hematologic Neoplasms - therapy</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Histocompatibility Testing</subject><subject>HLA Antigens - genetics</subject><subject>HLA Antigens - immunology</subject><subject>Humans</subject><subject>Infant</subject><subject>Infection - etiology</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Research Paper</subject><subject>Toll-Like Receptors - genetics</subject><subject>Transplantation, Homologous</subject><subject>Treatment Outcome</subject><subject>Unrelated Donors</subject><subject>Young Adult</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctOAzEMjBAIUOkHcEF75LJl89pNLkioPKVKXMo5ym6dEtgmJUmL-HuithTwxZZmbI89CJ3jaoRFTcmVd51POswhjXBDMT9Ap1gyWRLO6eGf-gQNY3yrcnDWCCKP0QkRTLBKklN0O_V9X_b2HYoAHSyTD8UcHCTbFWsdrE7Wu1hYV7TeQbHQIfjPIgXt4rLXLm3wM3RkdB9huMsD9HJ_Nx0_lpPnh6fxzaTsGCGpbAiA7Dg2M46xqTBoSRlhQprKAG0MbVrBeM10hSXMupbhpsUtJpWRM1PXQAfoejt3uWoXmQEuC-nVMtis60t5bdV_xNlXNfdrxXkWkJ80QJe7AcF_rCAmtbCxgz5fAn4VFRayFlIQQTMVb6ld8DEGMPs1uFIbA9SvAWpjQO65-Ktv3_HzbvoNnEKGNw</recordid><startdate>20170711</startdate><enddate>20170711</enddate><creator>Uchino, Kaori</creator><creator>Mizuno, Shohei</creator><creator>Sato-Otsubo, Aiko</creator><creator>Nannya, Yasuhito</creator><creator>Mizutani, Motonori</creator><creator>Horio, Tomohiro</creator><creator>Hanamura, Ichiro</creator><creator>Espinoza, J Luis</creator><creator>Onizuka, Makoto</creator><creator>Kashiwase, Koichi</creator><creator>Morishima, Yasuo</creator><creator>Fukuda, Takahiro</creator><creator>Kodera, Yoshihisa</creator><creator>Doki, Noriko</creator><creator>Miyamura, Koichi</creator><creator>Mori, Takehiko</creator><creator>Ogawa, Seishi</creator><creator>Takami, Akiyoshi</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>20170711</creationdate><title>Toll-like receptor genetic variations in bone marrow transplantation</title><author>Uchino, Kaori ; Mizuno, Shohei ; Sato-Otsubo, Aiko ; Nannya, Yasuhito ; Mizutani, Motonori ; Horio, Tomohiro ; Hanamura, Ichiro ; Espinoza, J Luis ; Onizuka, Makoto ; Kashiwase, Koichi ; Morishima, Yasuo ; Fukuda, Takahiro ; Kodera, Yoshihisa ; Doki, Noriko ; Miyamura, Koichi ; Mori, Takehiko ; Ogawa, Seishi ; Takami, Akiyoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-72ee9c51fd511f01ea9342489f0fe37f37b84564a019edcb417b1b120f9df66e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Alleles</topic><topic>Bone Marrow Transplantation - adverse effects</topic><topic>Bone Marrow Transplantation - methods</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>Genetic Variation</topic><topic>Genotype</topic><topic>Graft vs Host Disease - diagnosis</topic><topic>Graft vs Host Disease - etiology</topic><topic>Hematologic Neoplasms - genetics</topic><topic>Hematologic Neoplasms - therapy</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Histocompatibility Testing</topic><topic>HLA Antigens - genetics</topic><topic>HLA Antigens - immunology</topic><topic>Humans</topic><topic>Infant</topic><topic>Infection - etiology</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Research Paper</topic><topic>Toll-Like Receptors - genetics</topic><topic>Transplantation, Homologous</topic><topic>Treatment Outcome</topic><topic>Unrelated Donors</topic><topic>Young Adult</topic><toplevel>online_resources</toplevel><creatorcontrib>Uchino, Kaori</creatorcontrib><creatorcontrib>Mizuno, Shohei</creatorcontrib><creatorcontrib>Sato-Otsubo, Aiko</creatorcontrib><creatorcontrib>Nannya, Yasuhito</creatorcontrib><creatorcontrib>Mizutani, Motonori</creatorcontrib><creatorcontrib>Horio, Tomohiro</creatorcontrib><creatorcontrib>Hanamura, Ichiro</creatorcontrib><creatorcontrib>Espinoza, J Luis</creatorcontrib><creatorcontrib>Onizuka, Makoto</creatorcontrib><creatorcontrib>Kashiwase, Koichi</creatorcontrib><creatorcontrib>Morishima, Yasuo</creatorcontrib><creatorcontrib>Fukuda, Takahiro</creatorcontrib><creatorcontrib>Kodera, Yoshihisa</creatorcontrib><creatorcontrib>Doki, Noriko</creatorcontrib><creatorcontrib>Miyamura, Koichi</creatorcontrib><creatorcontrib>Mori, Takehiko</creatorcontrib><creatorcontrib>Ogawa, Seishi</creatorcontrib><creatorcontrib>Takami, Akiyoshi</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>Uchino, Kaori</au><au>Mizuno, Shohei</au><au>Sato-Otsubo, Aiko</au><au>Nannya, Yasuhito</au><au>Mizutani, Motonori</au><au>Horio, Tomohiro</au><au>Hanamura, Ichiro</au><au>Espinoza, J Luis</au><au>Onizuka, Makoto</au><au>Kashiwase, Koichi</au><au>Morishima, Yasuo</au><au>Fukuda, Takahiro</au><au>Kodera, Yoshihisa</au><au>Doki, Noriko</au><au>Miyamura, Koichi</au><au>Mori, Takehiko</au><au>Ogawa, Seishi</au><au>Takami, Akiyoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Toll-like receptor genetic variations in bone marrow transplantation</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-07-11</date><risdate>2017</risdate><volume>8</volume><issue>28</issue><spage>45670</spage><epage>45686</epage><pages>45670-45686</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>The Toll-like receptor family mediates the innate immune system through recognizing the molecular patterns of microorganisms and self-components and leading the synthesis of the inflammatory mediators. We retrospectively examined whether or not genetic variations in toll-like receptor 1 (rs5743551, -7202GQ>A), toll-like receptor 2 (rs7656411, 22215G>T), and toll-like receptor 4 (rs11536889, +3725G>C) affected transplant outcomes in a cohort of 365 patients who underwent unrelated HLA-matched bone marrow transplantation (for hematologic malignancies through the Japan Marrow Donor Program. Only donor toll-like receptor 4 variation significantly improved the survival outcomes. A multivariate analysis showed that the donor toll-like receptor 4 +3725G/G genotype was significantly associated with a better 5-year progression-free survival and a lower 5-year transplant-related mortality than other variations. Furthermore, the donor toll-like receptor 4 +3725G/G genotype was associated with a significantly lower incidence of fatal infections than other variations. The validation study of 502 patients confirmed that the donor toll-like receptor 4 +3725G/G genotype was associated with better survival outcomes. Toll-like receptor4 genotyping in transplant donors may therefore be a useful tool for optimizing donor selection and evaluating pretransplantation risks.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28484092</pmid><doi>10.18632/oncotarget.17315</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Alleles Bone Marrow Transplantation - adverse effects Bone Marrow Transplantation - methods Child Child, Preschool Female Gene Frequency Genetic Variation Genotype Graft vs Host Disease - diagnosis Graft vs Host Disease - etiology Hematologic Neoplasms - genetics Hematologic Neoplasms - therapy Hematopoietic Stem Cell Transplantation Histocompatibility Testing HLA Antigens - genetics HLA Antigens - immunology Humans Infant Infection - etiology Kaplan-Meier Estimate Male Middle Aged Polymorphism, Single Nucleotide Research Paper Toll-Like Receptors - genetics Transplantation, Homologous Treatment Outcome Unrelated Donors Young Adult |
| title | Toll-like receptor genetic variations in bone marrow transplantation |
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