Genomewide Association Study of an AIDS-Nonprogression Cohort Emphasizes the Role Played by HLA Genes (ANRS Genomewide Association Study 02)
To elucidate the genetic factors predisposing to AIDS progression, we analyzed a unique cohort of 275 human immunodeficiency virus (HIV) type 1-seropositive nonprogressor patients in relation to a control group of 1352 seronegative individuals in a genomewide association study (GWAS). The strongest...
Gespeichert in:
| Veröffentlicht in: | The Journal of infectious diseases 2009-02, Vol.199 (3), p.419-426 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 426 |
|---|---|
| container_issue | 3 |
| container_start_page | 419 |
| container_title | The Journal of infectious diseases |
| container_volume | 199 |
| creator | Limou, Sophie Le Clerc, Sigrid Coulonges, Cédric Carpentier, Wassila Dina, Christian Delameau, Olivier Labib, Taoufik Taing, Lieng Sladek, Rob Deveau, Christiane Ratsimandresy, Rojo Montes, Matthieu Spadoni, Jean-Loius Leliè, Jean-Daniel Lévy, Yves Therwath, Amu Schächter, François Matsuda, Fumihiko Gut, Ivo Froguel, Philippe Delfraissy, Jean-François Hercberg, Serge Zagury, Jean-François |
| description | To elucidate the genetic factors predisposing to AIDS progression, we analyzed a unique cohort of 275 human immunodeficiency virus (HIV) type 1-seropositive nonprogressor patients in relation to a control group of 1352 seronegative individuals in a genomewide association study (GWAS). The strongest association was obtained for HCP5 rs2395029 (P = 6.79 × 10−10; odds ratio, 3.47) andwaspossibly linkedto aneffect of sex. Interestingly, this single-nucleotide polymorphism (SNP) was in high linkage disequilibrium with HLA-B, MICB, TNF, and several other HLA locus SNPs and haplotypes. A meta-analysis of our genomic data combined with data from the previously conducted Euro-CHAVI (Center for HIV/AIDS Vaccine Immunology) GWAS confirmed the HCP5 signal (P = 3.02 × 10−19) and identified several new associations, all of them involving HLA genes: MICB, TNF, RDBP, BAT1-5, PSORS1C1, and HLA-C. Finally, stratification by HCP5 rs2395029 genotypes emphasized an independent role for ZNRD1, also in the HLA locus, and this finding was confirmed by experimental data. The present study, the first GWAS of HIV-1 nonprogressors, underscores the potential for some HLA genes to control disease progression soon after infection. |
| doi_str_mv | 10.1086/596067 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_02566791v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>40254435</jstor_id><oup_id>10.1086/596067</oup_id><sourcerecordid>40254435</sourcerecordid><originalsourceid>FETCH-LOGICAL-c427t-e356b538d6c772c3e1c949cc9cc855d81eb775a757cee206f7e63a0acf4fabff3</originalsourceid><addsrcrecordid>eNp9kVFv0zAUhS0EYmXAPwCZBxB7CNhxbCePUTfWSVWZVpAQL5bj3FCPJC52Mii_gR-Nq1TdE0iWruTz3XN1dBB6Tsk7SnLxnheCCPkAzShnMhGCsodoRkiaJjQvihP0JIRbQkjGhHyMTmhBKS-yYob-XELvOvhpa8BlCM5YPVjX4_Uw1jvsGqx7XF6dr5OV67feffMQwl6fu43zA77othsd7G8IeNgAvnEt4OtW76DG1Q4vliWO_lF8W65u1vi_t0h69hQ9anQb4NlhnqLPHy4-zRfJ8uPl1bxcJiZL5ZAA46LiLK-FkTI1DKiJWYyJL-e8zilUUnItuTQAKRGNBME00abJGl01DTtFZ5PvRrdq622n_U45bdWiXKr9H0m5ELKgdzSybyY2pv8xQhhUZ4OBttU9uDEoIXLKZS7uQeNdCB6aozMlat-RmjqK4MuD41h1UN9jh1Ii8PoA6GB023jdGxuOXEoJJzlnkXs1cW7c_vvYi4m5DYPzRyqLCbOM8agnk27DAL-OuvbfVdyWXC2-fFXsmlO-Ziu1Yn8B9Ca6bQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>66815786</pqid></control><display><type>article</type><title>Genomewide Association Study of an AIDS-Nonprogression Cohort Emphasizes the Role Played by HLA Genes (ANRS Genomewide Association Study 02)</title><source>MEDLINE</source><source>JSTOR Archive Collection A-Z Listing</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Limou, Sophie ; Le Clerc, Sigrid ; Coulonges, Cédric ; Carpentier, Wassila ; Dina, Christian ; Delameau, Olivier ; Labib, Taoufik ; Taing, Lieng ; Sladek, Rob ; Deveau, Christiane ; Ratsimandresy, Rojo ; Montes, Matthieu ; Spadoni, Jean-Loius ; Leliè, Jean-Daniel ; Lévy, Yves ; Therwath, Amu ; Schächter, François ; Matsuda, Fumihiko ; Gut, Ivo ; Froguel, Philippe ; Delfraissy, Jean-François ; Hercberg, Serge ; Zagury, Jean-François</creator><creatorcontrib>Limou, Sophie ; Le Clerc, Sigrid ; Coulonges, Cédric ; Carpentier, Wassila ; Dina, Christian ; Delameau, Olivier ; Labib, Taoufik ; Taing, Lieng ; Sladek, Rob ; Deveau, Christiane ; Ratsimandresy, Rojo ; Montes, Matthieu ; Spadoni, Jean-Loius ; Leliè, Jean-Daniel ; Lévy, Yves ; Therwath, Amu ; Schächter, François ; Matsuda, Fumihiko ; Gut, Ivo ; Froguel, Philippe ; Delfraissy, Jean-François ; Hercberg, Serge ; Zagury, Jean-François ; ANRS Genomic Group ; ANRS Genomic Group</creatorcontrib><description>To elucidate the genetic factors predisposing to AIDS progression, we analyzed a unique cohort of 275 human immunodeficiency virus (HIV) type 1-seropositive nonprogressor patients in relation to a control group of 1352 seronegative individuals in a genomewide association study (GWAS). The strongest association was obtained for HCP5 rs2395029 (P = 6.79 × 10−10; odds ratio, 3.47) andwaspossibly linkedto aneffect of sex. Interestingly, this single-nucleotide polymorphism (SNP) was in high linkage disequilibrium with HLA-B, MICB, TNF, and several other HLA locus SNPs and haplotypes. A meta-analysis of our genomic data combined with data from the previously conducted Euro-CHAVI (Center for HIV/AIDS Vaccine Immunology) GWAS confirmed the HCP5 signal (P = 3.02 × 10−19) and identified several new associations, all of them involving HLA genes: MICB, TNF, RDBP, BAT1-5, PSORS1C1, and HLA-C. Finally, stratification by HCP5 rs2395029 genotypes emphasized an independent role for ZNRD1, also in the HLA locus, and this finding was confirmed by experimental data. The present study, the first GWAS of HIV-1 nonprogressors, underscores the potential for some HLA genes to control disease progression soon after infection.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1086/596067</identifier><identifier>PMID: 19115949</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Oxford: The University of Chicago Press</publisher><subject>Acquired Immunodeficiency Syndrome - genetics ; AIDS ; Biological and medical sciences ; Cohort Studies ; Disease Progression ; Fundamental and applied biological sciences. Psychology ; Genetic loci ; Genome, Human ; Genomics ; Genotype ; Haplotypes ; HIV 1 ; HIV Seropositivity - genetics ; HIV/AIDS ; HLA antigens ; HLA Antigens - genetics ; Human health and pathology ; Human viral diseases ; Humans ; Infectious diseases ; Life Sciences ; Linkage Disequilibrium ; Major Histocompatibility Complex - genetics ; Medical genetics ; Medical sciences ; Microbiology ; P values ; Polymorphism, Single Nucleotide ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Viral load</subject><ispartof>The Journal of infectious diseases, 2009-02, Vol.199 (3), p.419-426</ispartof><rights>Copyright 2008 Infectious Diseases Society of America</rights><rights>2009 by the Infectious Diseases Society of America 2009</rights><rights>2009 INIST-CNRS</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-e356b538d6c772c3e1c949cc9cc855d81eb775a757cee206f7e63a0acf4fabff3</citedby><cites>FETCH-LOGICAL-c427t-e356b538d6c772c3e1c949cc9cc855d81eb775a757cee206f7e63a0acf4fabff3</cites><orcidid>0000-0003-4557-4553 ; 0000-0002-7702-8234 ; 0000-0001-5921-460X ; 0000-0002-7722-7348 ; 0000-0002-3906-8446 ; 0000-0002-3168-1350</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/40254435$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/40254435$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,781,785,804,886,27926,27927,58019,58252</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21050853$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19115949$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.sorbonne-universite.fr/hal-02566791$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Limou, Sophie</creatorcontrib><creatorcontrib>Le Clerc, Sigrid</creatorcontrib><creatorcontrib>Coulonges, Cédric</creatorcontrib><creatorcontrib>Carpentier, Wassila</creatorcontrib><creatorcontrib>Dina, Christian</creatorcontrib><creatorcontrib>Delameau, Olivier</creatorcontrib><creatorcontrib>Labib, Taoufik</creatorcontrib><creatorcontrib>Taing, Lieng</creatorcontrib><creatorcontrib>Sladek, Rob</creatorcontrib><creatorcontrib>Deveau, Christiane</creatorcontrib><creatorcontrib>Ratsimandresy, Rojo</creatorcontrib><creatorcontrib>Montes, Matthieu</creatorcontrib><creatorcontrib>Spadoni, Jean-Loius</creatorcontrib><creatorcontrib>Leliè, Jean-Daniel</creatorcontrib><creatorcontrib>Lévy, Yves</creatorcontrib><creatorcontrib>Therwath, Amu</creatorcontrib><creatorcontrib>Schächter, François</creatorcontrib><creatorcontrib>Matsuda, Fumihiko</creatorcontrib><creatorcontrib>Gut, Ivo</creatorcontrib><creatorcontrib>Froguel, Philippe</creatorcontrib><creatorcontrib>Delfraissy, Jean-François</creatorcontrib><creatorcontrib>Hercberg, Serge</creatorcontrib><creatorcontrib>Zagury, Jean-François</creatorcontrib><creatorcontrib>ANRS Genomic Group</creatorcontrib><creatorcontrib>ANRS Genomic Group</creatorcontrib><title>Genomewide Association Study of an AIDS-Nonprogression Cohort Emphasizes the Role Played by HLA Genes (ANRS Genomewide Association Study 02)</title><title>The Journal of infectious diseases</title><addtitle>The Journal of Infectious Diseases</addtitle><addtitle>The Journal of Infectious Diseases</addtitle><description>To elucidate the genetic factors predisposing to AIDS progression, we analyzed a unique cohort of 275 human immunodeficiency virus (HIV) type 1-seropositive nonprogressor patients in relation to a control group of 1352 seronegative individuals in a genomewide association study (GWAS). The strongest association was obtained for HCP5 rs2395029 (P = 6.79 × 10−10; odds ratio, 3.47) andwaspossibly linkedto aneffect of sex. Interestingly, this single-nucleotide polymorphism (SNP) was in high linkage disequilibrium with HLA-B, MICB, TNF, and several other HLA locus SNPs and haplotypes. A meta-analysis of our genomic data combined with data from the previously conducted Euro-CHAVI (Center for HIV/AIDS Vaccine Immunology) GWAS confirmed the HCP5 signal (P = 3.02 × 10−19) and identified several new associations, all of them involving HLA genes: MICB, TNF, RDBP, BAT1-5, PSORS1C1, and HLA-C. Finally, stratification by HCP5 rs2395029 genotypes emphasized an independent role for ZNRD1, also in the HLA locus, and this finding was confirmed by experimental data. The present study, the first GWAS of HIV-1 nonprogressors, underscores the potential for some HLA genes to control disease progression soon after infection.</description><subject>Acquired Immunodeficiency Syndrome - genetics</subject><subject>AIDS</subject><subject>Biological and medical sciences</subject><subject>Cohort Studies</subject><subject>Disease Progression</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic loci</subject><subject>Genome, Human</subject><subject>Genomics</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>HIV 1</subject><subject>HIV Seropositivity - genetics</subject><subject>HIV/AIDS</subject><subject>HLA antigens</subject><subject>HLA Antigens - genetics</subject><subject>Human health and pathology</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Life Sciences</subject><subject>Linkage Disequilibrium</subject><subject>Major Histocompatibility Complex - genetics</subject><subject>Medical genetics</subject><subject>Medical sciences</subject><subject>Microbiology</subject><subject>P values</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><subject>Viral load</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kVFv0zAUhS0EYmXAPwCZBxB7CNhxbCePUTfWSVWZVpAQL5bj3FCPJC52Mii_gR-Nq1TdE0iWruTz3XN1dBB6Tsk7SnLxnheCCPkAzShnMhGCsodoRkiaJjQvihP0JIRbQkjGhHyMTmhBKS-yYob-XELvOvhpa8BlCM5YPVjX4_Uw1jvsGqx7XF6dr5OV67feffMQwl6fu43zA77othsd7G8IeNgAvnEt4OtW76DG1Q4vliWO_lF8W65u1vi_t0h69hQ9anQb4NlhnqLPHy4-zRfJ8uPl1bxcJiZL5ZAA46LiLK-FkTI1DKiJWYyJL-e8zilUUnItuTQAKRGNBME00abJGl01DTtFZ5PvRrdq622n_U45bdWiXKr9H0m5ELKgdzSybyY2pv8xQhhUZ4OBttU9uDEoIXLKZS7uQeNdCB6aozMlat-RmjqK4MuD41h1UN9jh1Ii8PoA6GB023jdGxuOXEoJJzlnkXs1cW7c_vvYi4m5DYPzRyqLCbOM8agnk27DAL-OuvbfVdyWXC2-fFXsmlO-Ziu1Yn8B9Ca6bQ</recordid><startdate>20090201</startdate><enddate>20090201</enddate><creator>Limou, Sophie</creator><creator>Le Clerc, Sigrid</creator><creator>Coulonges, Cédric</creator><creator>Carpentier, Wassila</creator><creator>Dina, Christian</creator><creator>Delameau, Olivier</creator><creator>Labib, Taoufik</creator><creator>Taing, Lieng</creator><creator>Sladek, Rob</creator><creator>Deveau, Christiane</creator><creator>Ratsimandresy, Rojo</creator><creator>Montes, Matthieu</creator><creator>Spadoni, Jean-Loius</creator><creator>Leliè, Jean-Daniel</creator><creator>Lévy, Yves</creator><creator>Therwath, Amu</creator><creator>Schächter, François</creator><creator>Matsuda, Fumihiko</creator><creator>Gut, Ivo</creator><creator>Froguel, Philippe</creator><creator>Delfraissy, Jean-François</creator><creator>Hercberg, Serge</creator><creator>Zagury, Jean-François</creator><general>The University of Chicago Press</general><general>University of Chicago Press</general><general>Oxford University Press</general><scope>BSCLL</scope><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>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0003-4557-4553</orcidid><orcidid>https://orcid.org/0000-0002-7702-8234</orcidid><orcidid>https://orcid.org/0000-0001-5921-460X</orcidid><orcidid>https://orcid.org/0000-0002-7722-7348</orcidid><orcidid>https://orcid.org/0000-0002-3906-8446</orcidid><orcidid>https://orcid.org/0000-0002-3168-1350</orcidid></search><sort><creationdate>20090201</creationdate><title>Genomewide Association Study of an AIDS-Nonprogression Cohort Emphasizes the Role Played by HLA Genes (ANRS Genomewide Association Study 02)</title><author>Limou, Sophie ; Le Clerc, Sigrid ; Coulonges, Cédric ; Carpentier, Wassila ; Dina, Christian ; Delameau, Olivier ; Labib, Taoufik ; Taing, Lieng ; Sladek, Rob ; Deveau, Christiane ; Ratsimandresy, Rojo ; Montes, Matthieu ; Spadoni, Jean-Loius ; Leliè, Jean-Daniel ; Lévy, Yves ; Therwath, Amu ; Schächter, François ; Matsuda, Fumihiko ; Gut, Ivo ; Froguel, Philippe ; Delfraissy, Jean-François ; Hercberg, Serge ; Zagury, Jean-François</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-e356b538d6c772c3e1c949cc9cc855d81eb775a757cee206f7e63a0acf4fabff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Acquired Immunodeficiency Syndrome - genetics</topic><topic>AIDS</topic><topic>Biological and medical sciences</topic><topic>Cohort Studies</topic><topic>Disease Progression</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetic loci</topic><topic>Genome, Human</topic><topic>Genomics</topic><topic>Genotype</topic><topic>Haplotypes</topic><topic>HIV 1</topic><topic>HIV Seropositivity - genetics</topic><topic>HIV/AIDS</topic><topic>HLA antigens</topic><topic>HLA Antigens - genetics</topic><topic>Human health and pathology</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Life Sciences</topic><topic>Linkage Disequilibrium</topic><topic>Major Histocompatibility Complex - genetics</topic><topic>Medical genetics</topic><topic>Medical sciences</topic><topic>Microbiology</topic><topic>P values</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><topic>Viral load</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Limou, Sophie</creatorcontrib><creatorcontrib>Le Clerc, Sigrid</creatorcontrib><creatorcontrib>Coulonges, Cédric</creatorcontrib><creatorcontrib>Carpentier, Wassila</creatorcontrib><creatorcontrib>Dina, Christian</creatorcontrib><creatorcontrib>Delameau, Olivier</creatorcontrib><creatorcontrib>Labib, Taoufik</creatorcontrib><creatorcontrib>Taing, Lieng</creatorcontrib><creatorcontrib>Sladek, Rob</creatorcontrib><creatorcontrib>Deveau, Christiane</creatorcontrib><creatorcontrib>Ratsimandresy, Rojo</creatorcontrib><creatorcontrib>Montes, Matthieu</creatorcontrib><creatorcontrib>Spadoni, Jean-Loius</creatorcontrib><creatorcontrib>Leliè, Jean-Daniel</creatorcontrib><creatorcontrib>Lévy, Yves</creatorcontrib><creatorcontrib>Therwath, Amu</creatorcontrib><creatorcontrib>Schächter, François</creatorcontrib><creatorcontrib>Matsuda, Fumihiko</creatorcontrib><creatorcontrib>Gut, Ivo</creatorcontrib><creatorcontrib>Froguel, Philippe</creatorcontrib><creatorcontrib>Delfraissy, Jean-François</creatorcontrib><creatorcontrib>Hercberg, Serge</creatorcontrib><creatorcontrib>Zagury, Jean-François</creatorcontrib><creatorcontrib>ANRS Genomic Group</creatorcontrib><creatorcontrib>ANRS Genomic Group</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><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>Hyper Article en Ligne (HAL)</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Limou, Sophie</au><au>Le Clerc, Sigrid</au><au>Coulonges, Cédric</au><au>Carpentier, Wassila</au><au>Dina, Christian</au><au>Delameau, Olivier</au><au>Labib, Taoufik</au><au>Taing, Lieng</au><au>Sladek, Rob</au><au>Deveau, Christiane</au><au>Ratsimandresy, Rojo</au><au>Montes, Matthieu</au><au>Spadoni, Jean-Loius</au><au>Leliè, Jean-Daniel</au><au>Lévy, Yves</au><au>Therwath, Amu</au><au>Schächter, François</au><au>Matsuda, Fumihiko</au><au>Gut, Ivo</au><au>Froguel, Philippe</au><au>Delfraissy, Jean-François</au><au>Hercberg, Serge</au><au>Zagury, Jean-François</au><aucorp>ANRS Genomic Group</aucorp><aucorp>ANRS Genomic Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomewide Association Study of an AIDS-Nonprogression Cohort Emphasizes the Role Played by HLA Genes (ANRS Genomewide Association Study 02)</atitle><jtitle>The Journal of infectious diseases</jtitle><stitle>The Journal of Infectious Diseases</stitle><addtitle>The Journal of Infectious Diseases</addtitle><date>2009-02-01</date><risdate>2009</risdate><volume>199</volume><issue>3</issue><spage>419</spage><epage>426</epage><pages>419-426</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>To elucidate the genetic factors predisposing to AIDS progression, we analyzed a unique cohort of 275 human immunodeficiency virus (HIV) type 1-seropositive nonprogressor patients in relation to a control group of 1352 seronegative individuals in a genomewide association study (GWAS). The strongest association was obtained for HCP5 rs2395029 (P = 6.79 × 10−10; odds ratio, 3.47) andwaspossibly linkedto aneffect of sex. Interestingly, this single-nucleotide polymorphism (SNP) was in high linkage disequilibrium with HLA-B, MICB, TNF, and several other HLA locus SNPs and haplotypes. A meta-analysis of our genomic data combined with data from the previously conducted Euro-CHAVI (Center for HIV/AIDS Vaccine Immunology) GWAS confirmed the HCP5 signal (P = 3.02 × 10−19) and identified several new associations, all of them involving HLA genes: MICB, TNF, RDBP, BAT1-5, PSORS1C1, and HLA-C. Finally, stratification by HCP5 rs2395029 genotypes emphasized an independent role for ZNRD1, also in the HLA locus, and this finding was confirmed by experimental data. The present study, the first GWAS of HIV-1 nonprogressors, underscores the potential for some HLA genes to control disease progression soon after infection.</abstract><cop>Oxford</cop><pub>The University of Chicago Press</pub><pmid>19115949</pmid><doi>10.1086/596067</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-4557-4553</orcidid><orcidid>https://orcid.org/0000-0002-7702-8234</orcidid><orcidid>https://orcid.org/0000-0001-5921-460X</orcidid><orcidid>https://orcid.org/0000-0002-7722-7348</orcidid><orcidid>https://orcid.org/0000-0002-3906-8446</orcidid><orcidid>https://orcid.org/0000-0002-3168-1350</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1899 |
| ispartof | The Journal of infectious diseases, 2009-02, Vol.199 (3), p.419-426 |
| issn | 0022-1899 1537-6613 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_02566791v1 |
| source | MEDLINE; JSTOR Archive Collection A-Z Listing; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Acquired Immunodeficiency Syndrome - genetics AIDS Biological and medical sciences Cohort Studies Disease Progression Fundamental and applied biological sciences. Psychology Genetic loci Genome, Human Genomics Genotype Haplotypes HIV 1 HIV Seropositivity - genetics HIV/AIDS HLA antigens HLA Antigens - genetics Human health and pathology Human viral diseases Humans Infectious diseases Life Sciences Linkage Disequilibrium Major Histocompatibility Complex - genetics Medical genetics Medical sciences Microbiology P values Polymorphism, Single Nucleotide Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral load |
| title | Genomewide Association Study of an AIDS-Nonprogression Cohort Emphasizes the Role Played by HLA Genes (ANRS Genomewide Association Study 02) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T07%3A45%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genomewide%20Association%20Study%20of%20an%20AIDS-Nonprogression%20Cohort%20Emphasizes%20the%20Role%20Played%20by%20HLA%20Genes%20(ANRS%20Genomewide%20Association%20Study%2002)&rft.jtitle=The%20Journal%20of%20infectious%20diseases&rft.au=Limou,%20Sophie&rft.aucorp=ANRS%20Genomic%20Group&rft.date=2009-02-01&rft.volume=199&rft.issue=3&rft.spage=419&rft.epage=426&rft.pages=419-426&rft.issn=0022-1899&rft.eissn=1537-6613&rft.coden=JIDIAQ&rft_id=info:doi/10.1086/596067&rft_dat=%3Cjstor_hal_p%3E40254435%3C/jstor_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=66815786&rft_id=info:pmid/19115949&rft_jstor_id=40254435&rft_oup_id=10.1086/596067&rfr_iscdi=true |