Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans
African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2010-08, Vol.329 (5993), p.841-845 |
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| creator | Genovese, Giulio Friedman, David J Ross, Michael D Lecordier, Laurence Uzureau, Pierrick Freedman, Barry I Bowden, Donald W Langefeld, Carl D Oleksyk, Taras K Uscinski Knob, Andrea L Bernhardy, Andrea J Hicks, Pamela J Nelson, George W Vanhollebeke, Benoit Winkler, Cheryl A Kopp, Jeffrey B Pays, Etienne Pollak, Martin R |
| description | African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans. |
| doi_str_mv | 10.1126/science.1193032 |
| format | Article |
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Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.</description><identifier>ISSN: 0036-8075</identifier><identifier>ISSN: 1095-9203</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1193032</identifier><identifier>PMID: 20647424</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Africa ; African Americans ; Alleles ; Apolipoprotein L1 ; Apolipoproteins - blood ; Apolipoproteins - genetics ; Apolipoproteins - metabolism ; Black or African American - genetics ; Case-Control Studies ; Chromosomes ; Cohort Studies ; Confidence intervals ; Diabetic nephropathies ; Disease risk ; Evolution ; Focal segmental glomerulosclerosis ; Gene Frequency ; Genes ; Genetic Association Studies ; Genetic mutation ; Genetic Predisposition to Disease ; Genotypes ; Glomerulosclerosis, Focal Segmental - ethnology ; Glomerulosclerosis, Focal Segmental - genetics ; Haplotypes ; Humans ; Hypertension - complications ; Immunity, Innate ; Kidney diseases ; Kidney Failure, Chronic - ethnology ; Kidney Failure, Chronic - etiology ; Kidney Failure, Chronic - genetics ; Kidneys ; Linkage Disequilibrium ; Lipoproteins, HDL - blood ; Lipoproteins, HDL - genetics ; Lipoproteins, HDL - metabolism ; Logistic Models ; Molecular Motor Proteins - genetics ; Mutation ; Myosin Heavy Chains - genetics ; Polymorphism, Single Nucleotide ; Population genetics ; Proteins ; Recombinant Proteins - metabolism ; Selection, Genetic ; Sequence Deletion ; Signatures ; Survival ; Trypanosoma brucei rhodesiense - metabolism ; Trypanosome ; Trypanosomiasis, African - genetics ; Trypanosomiasis, African - parasitology</subject><ispartof>Science (American Association for the Advancement of Science), 2010-08, Vol.329 (5993), p.841-845</ispartof><rights>2010 American Association for the Advancement of Science</rights><rights>Copyright © 2010, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c497t-c2218ad8c843e5217f516d72c36f4013cfda97db69c57e4e85a88b1f3e983df23</citedby><cites>FETCH-LOGICAL-c497t-c2218ad8c843e5217f516d72c36f4013cfda97db69c57e4e85a88b1f3e983df23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/40799745$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/40799745$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,776,780,799,881,2870,2871,27903,27904,57995,58228</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20647424$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Genovese, Giulio</creatorcontrib><creatorcontrib>Friedman, David J</creatorcontrib><creatorcontrib>Ross, Michael D</creatorcontrib><creatorcontrib>Lecordier, Laurence</creatorcontrib><creatorcontrib>Uzureau, Pierrick</creatorcontrib><creatorcontrib>Freedman, Barry I</creatorcontrib><creatorcontrib>Bowden, Donald W</creatorcontrib><creatorcontrib>Langefeld, Carl D</creatorcontrib><creatorcontrib>Oleksyk, Taras K</creatorcontrib><creatorcontrib>Uscinski Knob, Andrea L</creatorcontrib><creatorcontrib>Bernhardy, Andrea J</creatorcontrib><creatorcontrib>Hicks, Pamela J</creatorcontrib><creatorcontrib>Nelson, George W</creatorcontrib><creatorcontrib>Vanhollebeke, Benoit</creatorcontrib><creatorcontrib>Winkler, Cheryl A</creatorcontrib><creatorcontrib>Kopp, Jeffrey B</creatorcontrib><creatorcontrib>Pays, Etienne</creatorcontrib><creatorcontrib>Pollak, Martin R</creatorcontrib><title>Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.</description><subject>Africa</subject><subject>African Americans</subject><subject>Alleles</subject><subject>Apolipoprotein L1</subject><subject>Apolipoproteins - blood</subject><subject>Apolipoproteins - genetics</subject><subject>Apolipoproteins - metabolism</subject><subject>Black or African American - genetics</subject><subject>Case-Control Studies</subject><subject>Chromosomes</subject><subject>Cohort Studies</subject><subject>Confidence intervals</subject><subject>Diabetic nephropathies</subject><subject>Disease risk</subject><subject>Evolution</subject><subject>Focal segmental glomerulosclerosis</subject><subject>Gene Frequency</subject><subject>Genes</subject><subject>Genetic Association Studies</subject><subject>Genetic mutation</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotypes</subject><subject>Glomerulosclerosis, Focal Segmental - ethnology</subject><subject>Glomerulosclerosis, Focal Segmental - genetics</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Hypertension - complications</subject><subject>Immunity, Innate</subject><subject>Kidney diseases</subject><subject>Kidney Failure, Chronic - ethnology</subject><subject>Kidney Failure, Chronic - etiology</subject><subject>Kidney Failure, Chronic - genetics</subject><subject>Kidneys</subject><subject>Linkage Disequilibrium</subject><subject>Lipoproteins, HDL - blood</subject><subject>Lipoproteins, HDL - genetics</subject><subject>Lipoproteins, HDL - metabolism</subject><subject>Logistic Models</subject><subject>Molecular Motor Proteins - genetics</subject><subject>Mutation</subject><subject>Myosin Heavy Chains - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population genetics</subject><subject>Proteins</subject><subject>Recombinant Proteins - metabolism</subject><subject>Selection, Genetic</subject><subject>Sequence Deletion</subject><subject>Signatures</subject><subject>Survival</subject><subject>Trypanosoma brucei rhodesiense - metabolism</subject><subject>Trypanosome</subject><subject>Trypanosomiasis, African - genetics</subject><subject>Trypanosomiasis, African - parasitology</subject><issn>0036-8075</issn><issn>1095-9203</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkbtvUzEYxa0KRENg7gS1WJhu6_djqRSVp4jUoS2r5fjaraMbO7VvivLfY0iIoAvTZ-v8fGyfA8AJRmcYE3FeXfTJ-bbRFFFyBCYYad5pgugzMEGIik4hyY_By1qXCDVN0xfgmCDBJCNsAq5ntWYX7RhzgjnAm7Jd25SH7RgdnK3zHMPvtkSbxgp_xPEefot98lv4IVZvq4cxwVko0dk2V_73or4Cz4Mdqn-9n1Nw--njzeWXbn71-evlbN45puXYOUKwsr1yilHPCZaBY9FL4qgIDGHqQm-17BdCOy4984pbpRY4UK8V7QOhU3Cx811vFivfO5_GYgezLnFly9ZkG82_Sor35i4_GqIVapc2g_d7g5IfNr6OZhWr88Ngk8-baqSSmAsh5P9JpjQTrMU-Be-ekMu8Kanl0KDWGWaYNeh8B7mSay0-HB6NkflVrNkXa_bFthNv__7rgf_TZAPe7IBlHXM56AxJrSXjTT_d6cFmY-9KrOb2mrSYEVZSKsTpT_53suc</recordid><startdate>20100813</startdate><enddate>20100813</enddate><creator>Genovese, Giulio</creator><creator>Friedman, David J</creator><creator>Ross, Michael D</creator><creator>Lecordier, Laurence</creator><creator>Uzureau, Pierrick</creator><creator>Freedman, Barry I</creator><creator>Bowden, Donald W</creator><creator>Langefeld, Carl D</creator><creator>Oleksyk, Taras K</creator><creator>Uscinski Knob, Andrea L</creator><creator>Bernhardy, Andrea J</creator><creator>Hicks, Pamela J</creator><creator>Nelson, George W</creator><creator>Vanhollebeke, Benoit</creator><creator>Winkler, Cheryl A</creator><creator>Kopp, Jeffrey B</creator><creator>Pays, Etienne</creator><creator>Pollak, Martin R</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>FBQ</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>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100813</creationdate><title>Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans</title><author>Genovese, Giulio ; Friedman, David J ; Ross, Michael D ; Lecordier, Laurence ; Uzureau, Pierrick ; Freedman, Barry I ; Bowden, Donald W ; Langefeld, Carl D ; Oleksyk, Taras K ; Uscinski Knob, Andrea L ; Bernhardy, Andrea J ; Hicks, Pamela J ; Nelson, George W ; Vanhollebeke, Benoit ; Winkler, Cheryl A ; Kopp, Jeffrey B ; Pays, Etienne ; Pollak, Martin R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c497t-c2218ad8c843e5217f516d72c36f4013cfda97db69c57e4e85a88b1f3e983df23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Africa</topic><topic>African Americans</topic><topic>Alleles</topic><topic>Apolipoprotein L1</topic><topic>Apolipoproteins - blood</topic><topic>Apolipoproteins - genetics</topic><topic>Apolipoproteins - metabolism</topic><topic>Black or African American - genetics</topic><topic>Case-Control Studies</topic><topic>Chromosomes</topic><topic>Cohort Studies</topic><topic>Confidence intervals</topic><topic>Diabetic nephropathies</topic><topic>Disease risk</topic><topic>Evolution</topic><topic>Focal segmental glomerulosclerosis</topic><topic>Gene Frequency</topic><topic>Genes</topic><topic>Genetic Association Studies</topic><topic>Genetic mutation</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotypes</topic><topic>Glomerulosclerosis, Focal Segmental - ethnology</topic><topic>Glomerulosclerosis, Focal Segmental - genetics</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Hypertension - complications</topic><topic>Immunity, Innate</topic><topic>Kidney diseases</topic><topic>Kidney Failure, Chronic - ethnology</topic><topic>Kidney Failure, Chronic - etiology</topic><topic>Kidney Failure, Chronic - genetics</topic><topic>Kidneys</topic><topic>Linkage Disequilibrium</topic><topic>Lipoproteins, HDL - blood</topic><topic>Lipoproteins, HDL - genetics</topic><topic>Lipoproteins, HDL - metabolism</topic><topic>Logistic Models</topic><topic>Molecular Motor Proteins - genetics</topic><topic>Mutation</topic><topic>Myosin Heavy Chains - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population genetics</topic><topic>Proteins</topic><topic>Recombinant Proteins - metabolism</topic><topic>Selection, Genetic</topic><topic>Sequence Deletion</topic><topic>Signatures</topic><topic>Survival</topic><topic>Trypanosoma brucei rhodesiense - metabolism</topic><topic>Trypanosome</topic><topic>Trypanosomiasis, African - genetics</topic><topic>Trypanosomiasis, African - parasitology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Genovese, Giulio</creatorcontrib><creatorcontrib>Friedman, David J</creatorcontrib><creatorcontrib>Ross, Michael D</creatorcontrib><creatorcontrib>Lecordier, Laurence</creatorcontrib><creatorcontrib>Uzureau, Pierrick</creatorcontrib><creatorcontrib>Freedman, Barry I</creatorcontrib><creatorcontrib>Bowden, Donald W</creatorcontrib><creatorcontrib>Langefeld, Carl D</creatorcontrib><creatorcontrib>Oleksyk, Taras K</creatorcontrib><creatorcontrib>Uscinski Knob, Andrea L</creatorcontrib><creatorcontrib>Bernhardy, Andrea J</creatorcontrib><creatorcontrib>Hicks, Pamela J</creatorcontrib><creatorcontrib>Nelson, George W</creatorcontrib><creatorcontrib>Vanhollebeke, Benoit</creatorcontrib><creatorcontrib>Winkler, Cheryl A</creatorcontrib><creatorcontrib>Kopp, Jeffrey B</creatorcontrib><creatorcontrib>Pays, Etienne</creatorcontrib><creatorcontrib>Pollak, Martin R</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Genovese, Giulio</au><au>Friedman, David J</au><au>Ross, Michael D</au><au>Lecordier, Laurence</au><au>Uzureau, Pierrick</au><au>Freedman, Barry I</au><au>Bowden, Donald W</au><au>Langefeld, Carl D</au><au>Oleksyk, Taras K</au><au>Uscinski Knob, Andrea L</au><au>Bernhardy, Andrea J</au><au>Hicks, Pamela J</au><au>Nelson, George W</au><au>Vanhollebeke, Benoit</au><au>Winkler, Cheryl A</au><au>Kopp, Jeffrey B</au><au>Pays, Etienne</au><au>Pollak, Martin R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2010-08-13</date><risdate>2010</risdate><volume>329</volume><issue>5993</issue><spage>841</spage><epage>845</epage><pages>841-845</pages><issn>0036-8075</issn><issn>1095-9203</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>20647424</pmid><doi>10.1126/science.1193032</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Africa African Americans Alleles Apolipoprotein L1 Apolipoproteins - blood Apolipoproteins - genetics Apolipoproteins - metabolism Black or African American - genetics Case-Control Studies Chromosomes Cohort Studies Confidence intervals Diabetic nephropathies Disease risk Evolution Focal segmental glomerulosclerosis Gene Frequency Genes Genetic Association Studies Genetic mutation Genetic Predisposition to Disease Genotypes Glomerulosclerosis, Focal Segmental - ethnology Glomerulosclerosis, Focal Segmental - genetics Haplotypes Humans Hypertension - complications Immunity, Innate Kidney diseases Kidney Failure, Chronic - ethnology Kidney Failure, Chronic - etiology Kidney Failure, Chronic - genetics Kidneys Linkage Disequilibrium Lipoproteins, HDL - blood Lipoproteins, HDL - genetics Lipoproteins, HDL - metabolism Logistic Models Molecular Motor Proteins - genetics Mutation Myosin Heavy Chains - genetics Polymorphism, Single Nucleotide Population genetics Proteins Recombinant Proteins - metabolism Selection, Genetic Sequence Deletion Signatures Survival Trypanosoma brucei rhodesiense - metabolism Trypanosome Trypanosomiasis, African - genetics Trypanosomiasis, African - parasitology |
| title | Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans |
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