Functional haplotypes of PADI4 , encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis
Individuals with rheumatoid arthritis frequently have autoantibodies to citrullinated peptides, suggesting the involvement of the peptidylarginine deiminases citrullinating enzymes (encoded by PADI genes) in rheumatoid arthritis. Previous linkage studies have shown that a susceptibility locus for rh...
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| Veröffentlicht in: | Nature genetics 2003-08, Vol.34 (4), p.395-402 |
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| creator | Yamada, Ryo Suzuki, Akari Chang, Xiaotian Tokuhiro, Shinya Sawada, Tetsuji Suzuki, Masakatsu Nagasaki, Miyuki Nakayama-Hamada, Makiko Kawaida, Reimi Ono, Mitsuru Ohtsuki, Masahiko Furukawa, Hidehiko Yoshino, Shinichi Yukioka, Masao Tohma, Shigeto Matsubara, Tsukasa Wakitani, Shigeyuki Teshima, Ryota Nishioka, Yuichi Sekine, Akihiro Iida, Aritoshi Takahashi, Atsushi Tsunoda, Tatsuhiko Nakamura, Yusuke Yamamoto, Kazuhiko |
| description | Individuals with rheumatoid arthritis frequently have autoantibodies to citrullinated peptides, suggesting the involvement of the peptidylarginine deiminases citrullinating enzymes (encoded by
PADI
genes) in rheumatoid arthritis. Previous linkage studies have shown that a susceptibility locus for rheumatoid arthritis includes four
PADI
genes but did not establish which
PADI
gene confers susceptibility to rheumatoid arthritis. We used a case-control linkage disequilibrium study to show that
PADI
type 4 is a susceptibility locus for rheumatoid arthritis (
P
= 0.000008).
PADI4
was expressed in hematological and rheumatoid arthritis synovial tissues. We also identified a haplotype of
PADI4
associated with susceptibility to rheumatoid arthritis that affected stability of transcripts and was associated with levels of antibody to citrullinated peptide in sera from individuals with rheumatoid arthritis. Our results imply that the
PADI4
haplotype associated with susceptibility to rheumatoid arthritis increases production of citrullinated peptides acting as autoantigens, resulting in heightened risk of developing the disease. |
| doi_str_mv | 10.1038/ng1206 |
| format | Article |
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PADI
genes) in rheumatoid arthritis. Previous linkage studies have shown that a susceptibility locus for rheumatoid arthritis includes four
PADI
genes but did not establish which
PADI
gene confers susceptibility to rheumatoid arthritis. We used a case-control linkage disequilibrium study to show that
PADI
type 4 is a susceptibility locus for rheumatoid arthritis (
P
= 0.000008).
PADI4
was expressed in hematological and rheumatoid arthritis synovial tissues. We also identified a haplotype of
PADI4
associated with susceptibility to rheumatoid arthritis that affected stability of transcripts and was associated with levels of antibody to citrullinated peptide in sera from individuals with rheumatoid arthritis. Our results imply that the
PADI4
haplotype associated with susceptibility to rheumatoid arthritis increases production of citrullinated peptides acting as autoantigens, resulting in heightened risk of developing the disease.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng1206</identifier><identifier>PMID: 12833157</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Agriculture ; Animal Genetics and Genomics ; Antibodies ; Arthritis, Rheumatoid - enzymology ; Arthritis, Rheumatoid - genetics ; Arthritis, Rheumatoid - immunology ; Autoantibodies - blood ; Autoantigens - chemistry ; Autoantigens - metabolism ; Autoimmune diseases ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Bone surgery ; Cancer Research ; Case-Control Studies ; Cell physiology ; Chemical research ; Chromosomes, Human, Pair 1 - genetics ; Citrulline - chemistry ; Citrulline - metabolism ; Diagnosis ; Disease ; Diseases of the osteoarticular system ; Enzymes ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Function ; Genes ; Genetic aspects ; Genomes ; Haplotypes ; Hematology ; Hospitals ; Human Genetics ; Humans ; Hydrolases - genetics ; Hydrolases - metabolism ; Inflammatory joint diseases ; Intermediate Filament Proteins - chemistry ; Intermediate Filament Proteins - immunology ; Intermediate Filament Proteins - metabolism ; Linkage Disequilibrium ; Male ; Medical sciences ; Middle Aged ; Molecular and cellular biology ; Peptides ; Peptides - chemistry ; Peptides - immunology ; Peptides - metabolism ; Physiological aspects ; Polymorphism, Single Nucleotide ; Protein-Arginine Deiminases ; Rheumatoid arthritis ; Risk factors ; RNA Stability ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Signal transduction ; Single nucleotide polymorphisms</subject><ispartof>Nature genetics, 2003-08, Vol.34 (4), p.395-402</ispartof><rights>Springer Nature America, Inc. 2003</rights><rights>2003 INIST-CNRS</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c551t-51d016ee595066a76af853e42be6a754f30041b32deca33b30e250f15116cc0b3</citedby><cites>FETCH-LOGICAL-c551t-51d016ee595066a76af853e42be6a754f30041b32deca33b30e250f15116cc0b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15048558$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12833157$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamada, Ryo</creatorcontrib><creatorcontrib>Suzuki, Akari</creatorcontrib><creatorcontrib>Chang, Xiaotian</creatorcontrib><creatorcontrib>Tokuhiro, Shinya</creatorcontrib><creatorcontrib>Sawada, Tetsuji</creatorcontrib><creatorcontrib>Suzuki, Masakatsu</creatorcontrib><creatorcontrib>Nagasaki, Miyuki</creatorcontrib><creatorcontrib>Nakayama-Hamada, Makiko</creatorcontrib><creatorcontrib>Kawaida, Reimi</creatorcontrib><creatorcontrib>Ono, Mitsuru</creatorcontrib><creatorcontrib>Ohtsuki, Masahiko</creatorcontrib><creatorcontrib>Furukawa, Hidehiko</creatorcontrib><creatorcontrib>Yoshino, Shinichi</creatorcontrib><creatorcontrib>Yukioka, Masao</creatorcontrib><creatorcontrib>Tohma, Shigeto</creatorcontrib><creatorcontrib>Matsubara, Tsukasa</creatorcontrib><creatorcontrib>Wakitani, Shigeyuki</creatorcontrib><creatorcontrib>Teshima, Ryota</creatorcontrib><creatorcontrib>Nishioka, Yuichi</creatorcontrib><creatorcontrib>Sekine, Akihiro</creatorcontrib><creatorcontrib>Iida, Aritoshi</creatorcontrib><creatorcontrib>Takahashi, Atsushi</creatorcontrib><creatorcontrib>Tsunoda, Tatsuhiko</creatorcontrib><creatorcontrib>Nakamura, Yusuke</creatorcontrib><creatorcontrib>Yamamoto, Kazuhiko</creatorcontrib><title>Functional haplotypes of PADI4 , encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Individuals with rheumatoid arthritis frequently have autoantibodies to citrullinated peptides, suggesting the involvement of the peptidylarginine deiminases citrullinating enzymes (encoded by
PADI
genes) in rheumatoid arthritis. Previous linkage studies have shown that a susceptibility locus for rheumatoid arthritis includes four
PADI
genes but did not establish which
PADI
gene confers susceptibility to rheumatoid arthritis. We used a case-control linkage disequilibrium study to show that
PADI
type 4 is a susceptibility locus for rheumatoid arthritis (
P
= 0.000008).
PADI4
was expressed in hematological and rheumatoid arthritis synovial tissues. We also identified a haplotype of
PADI4
associated with susceptibility to rheumatoid arthritis that affected stability of transcripts and was associated with levels of antibody to citrullinated peptide in sera from individuals with rheumatoid arthritis. Our results imply that the
PADI4
haplotype associated with susceptibility to rheumatoid arthritis increases production of citrullinated peptides acting as autoantigens, resulting in heightened risk of developing the disease.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Agriculture</subject><subject>Animal Genetics and Genomics</subject><subject>Antibodies</subject><subject>Arthritis, Rheumatoid - enzymology</subject><subject>Arthritis, Rheumatoid - genetics</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Autoantibodies - blood</subject><subject>Autoantigens - chemistry</subject><subject>Autoantigens - metabolism</subject><subject>Autoimmune diseases</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bone surgery</subject><subject>Cancer Research</subject><subject>Case-Control Studies</subject><subject>Cell physiology</subject><subject>Chemical research</subject><subject>Chromosomes, Human, Pair 1 - genetics</subject><subject>Citrulline - chemistry</subject><subject>Citrulline - metabolism</subject><subject>Diagnosis</subject><subject>Disease</subject><subject>Diseases of the osteoarticular system</subject><subject>Enzymes</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Function</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Haplotypes</subject><subject>Hematology</subject><subject>Hospitals</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Hydrolases - genetics</subject><subject>Hydrolases - metabolism</subject><subject>Inflammatory joint diseases</subject><subject>Intermediate Filament Proteins - chemistry</subject><subject>Intermediate Filament Proteins - immunology</subject><subject>Intermediate Filament Proteins - metabolism</subject><subject>Linkage Disequilibrium</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Molecular and cellular biology</subject><subject>Peptides</subject><subject>Peptides - chemistry</subject><subject>Peptides - immunology</subject><subject>Peptides - metabolism</subject><subject>Physiological aspects</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Protein-Arginine Deiminases</subject><subject>Rheumatoid arthritis</subject><subject>Risk factors</subject><subject>RNA Stability</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal transduction</subject><subject>Single nucleotide polymorphisms</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</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>eNqN0luL1DAUAOAiiruu-gtEwsoqwnZNmkuzj8Pq6sDCirfXkklPO1napCYp7vgD_N1maHEYFZQ85HK-c0LCybLHBJ8RTOUr25ICizvZIeFM5KQk8m5aY0Fyhqk4yB6EcIMxYQzL-9kBKSSlhJeH2Y_L0eponFUdWquhc3EzQECuQe8Xr5cMnSKw2tXGtkib6MeuM1bF7Rbs900PaIAhmnrTKd8aayygGkyfTADETpHygFQIThsVoUbfTFwjv4axV9GZOoXj2ptowsPsXqO6AI_m-Sj7fPnm08W7_Or67fJicZVrzknMOakxEQD8nGMhVClUIzkFVqwg7ThrKMaMrGhRg1aUriiGguOGcEKE1nhFj7LnU93Bu68jhFj1JmjoOmXBjaEqKZdUpPEvSKQkSZYJHv8Gb9zo03eGqigKIUshWELPJtSqDipjGxe90tuK1SKVYeS8YDKps7-oNGrojXYWGpPO9xJe7iUkE-E2tmoMoVp-_PD_9vrLvp0fr70LwUNTDd70ym8qgqttu1VTuyX4dH78uOqh3rG5vxI4mYEKWnWNV1absHMcM8n59sYXkwspZFvwu1_848onk0xtOHr4VWoO_wRLI_BZ</recordid><startdate>20030801</startdate><enddate>20030801</enddate><creator>Yamada, Ryo</creator><creator>Suzuki, Akari</creator><creator>Chang, Xiaotian</creator><creator>Tokuhiro, Shinya</creator><creator>Sawada, Tetsuji</creator><creator>Suzuki, Masakatsu</creator><creator>Nagasaki, Miyuki</creator><creator>Nakayama-Hamada, Makiko</creator><creator>Kawaida, Reimi</creator><creator>Ono, Mitsuru</creator><creator>Ohtsuki, Masahiko</creator><creator>Furukawa, Hidehiko</creator><creator>Yoshino, Shinichi</creator><creator>Yukioka, Masao</creator><creator>Tohma, Shigeto</creator><creator>Matsubara, Tsukasa</creator><creator>Wakitani, Shigeyuki</creator><creator>Teshima, Ryota</creator><creator>Nishioka, Yuichi</creator><creator>Sekine, Akihiro</creator><creator>Iida, Aritoshi</creator><creator>Takahashi, Atsushi</creator><creator>Tsunoda, Tatsuhiko</creator><creator>Nakamura, Yusuke</creator><creator>Yamamoto, Kazuhiko</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>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>7X8</scope></search><sort><creationdate>20030801</creationdate><title>Functional haplotypes of PADI4 , encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis</title><author>Yamada, Ryo ; Suzuki, Akari ; Chang, Xiaotian ; Tokuhiro, Shinya ; Sawada, Tetsuji ; Suzuki, Masakatsu ; Nagasaki, Miyuki ; Nakayama-Hamada, Makiko ; Kawaida, Reimi ; Ono, Mitsuru ; Ohtsuki, Masahiko ; Furukawa, Hidehiko ; Yoshino, Shinichi ; Yukioka, Masao ; Tohma, Shigeto ; Matsubara, Tsukasa ; Wakitani, Shigeyuki ; Teshima, Ryota ; Nishioka, Yuichi ; Sekine, Akihiro ; Iida, Aritoshi ; Takahashi, Atsushi ; Tsunoda, Tatsuhiko ; Nakamura, Yusuke ; Yamamoto, Kazuhiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c551t-51d016ee595066a76af853e42be6a754f30041b32deca33b30e250f15116cc0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Agriculture</topic><topic>Animal Genetics and Genomics</topic><topic>Antibodies</topic><topic>Arthritis, Rheumatoid - enzymology</topic><topic>Arthritis, Rheumatoid - genetics</topic><topic>Arthritis, Rheumatoid - immunology</topic><topic>Autoantibodies - blood</topic><topic>Autoantigens - chemistry</topic><topic>Autoantigens - metabolism</topic><topic>Autoimmune diseases</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bone surgery</topic><topic>Cancer Research</topic><topic>Case-Control Studies</topic><topic>Cell physiology</topic><topic>Chemical research</topic><topic>Chromosomes, Human, Pair 1 - genetics</topic><topic>Citrulline - chemistry</topic><topic>Citrulline - metabolism</topic><topic>Diagnosis</topic><topic>Disease</topic><topic>Diseases of the osteoarticular system</topic><topic>Enzymes</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Function</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Haplotypes</topic><topic>Hematology</topic><topic>Hospitals</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Hydrolases - genetics</topic><topic>Hydrolases - metabolism</topic><topic>Inflammatory joint diseases</topic><topic>Intermediate Filament Proteins - chemistry</topic><topic>Intermediate Filament Proteins - immunology</topic><topic>Intermediate Filament Proteins - metabolism</topic><topic>Linkage Disequilibrium</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Molecular and cellular biology</topic><topic>Peptides</topic><topic>Peptides - chemistry</topic><topic>Peptides - immunology</topic><topic>Peptides - metabolism</topic><topic>Physiological aspects</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Protein-Arginine Deiminases</topic><topic>Rheumatoid arthritis</topic><topic>Risk factors</topic><topic>RNA Stability</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal transduction</topic><topic>Single nucleotide polymorphisms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamada, Ryo</creatorcontrib><creatorcontrib>Suzuki, Akari</creatorcontrib><creatorcontrib>Chang, Xiaotian</creatorcontrib><creatorcontrib>Tokuhiro, Shinya</creatorcontrib><creatorcontrib>Sawada, Tetsuji</creatorcontrib><creatorcontrib>Suzuki, Masakatsu</creatorcontrib><creatorcontrib>Nagasaki, Miyuki</creatorcontrib><creatorcontrib>Nakayama-Hamada, Makiko</creatorcontrib><creatorcontrib>Kawaida, Reimi</creatorcontrib><creatorcontrib>Ono, Mitsuru</creatorcontrib><creatorcontrib>Ohtsuki, Masahiko</creatorcontrib><creatorcontrib>Furukawa, Hidehiko</creatorcontrib><creatorcontrib>Yoshino, Shinichi</creatorcontrib><creatorcontrib>Yukioka, Masao</creatorcontrib><creatorcontrib>Tohma, Shigeto</creatorcontrib><creatorcontrib>Matsubara, Tsukasa</creatorcontrib><creatorcontrib>Wakitani, Shigeyuki</creatorcontrib><creatorcontrib>Teshima, Ryota</creatorcontrib><creatorcontrib>Nishioka, Yuichi</creatorcontrib><creatorcontrib>Sekine, Akihiro</creatorcontrib><creatorcontrib>Iida, Aritoshi</creatorcontrib><creatorcontrib>Takahashi, Atsushi</creatorcontrib><creatorcontrib>Tsunoda, Tatsuhiko</creatorcontrib><creatorcontrib>Nakamura, Yusuke</creatorcontrib><creatorcontrib>Yamamoto, Kazuhiko</creatorcontrib><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>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamada, Ryo</au><au>Suzuki, Akari</au><au>Chang, Xiaotian</au><au>Tokuhiro, Shinya</au><au>Sawada, Tetsuji</au><au>Suzuki, Masakatsu</au><au>Nagasaki, Miyuki</au><au>Nakayama-Hamada, Makiko</au><au>Kawaida, Reimi</au><au>Ono, Mitsuru</au><au>Ohtsuki, Masahiko</au><au>Furukawa, Hidehiko</au><au>Yoshino, Shinichi</au><au>Yukioka, Masao</au><au>Tohma, Shigeto</au><au>Matsubara, Tsukasa</au><au>Wakitani, Shigeyuki</au><au>Teshima, Ryota</au><au>Nishioka, Yuichi</au><au>Sekine, Akihiro</au><au>Iida, Aritoshi</au><au>Takahashi, Atsushi</au><au>Tsunoda, Tatsuhiko</au><au>Nakamura, Yusuke</au><au>Yamamoto, Kazuhiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional haplotypes of PADI4 , encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2003-08-01</date><risdate>2003</risdate><volume>34</volume><issue>4</issue><spage>395</spage><epage>402</epage><pages>395-402</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><coden>NGENEC</coden><abstract>Individuals with rheumatoid arthritis frequently have autoantibodies to citrullinated peptides, suggesting the involvement of the peptidylarginine deiminases citrullinating enzymes (encoded by
PADI
genes) in rheumatoid arthritis. Previous linkage studies have shown that a susceptibility locus for rheumatoid arthritis includes four
PADI
genes but did not establish which
PADI
gene confers susceptibility to rheumatoid arthritis. We used a case-control linkage disequilibrium study to show that
PADI
type 4 is a susceptibility locus for rheumatoid arthritis (
P
= 0.000008).
PADI4
was expressed in hematological and rheumatoid arthritis synovial tissues. We also identified a haplotype of
PADI4
associated with susceptibility to rheumatoid arthritis that affected stability of transcripts and was associated with levels of antibody to citrullinated peptide in sera from individuals with rheumatoid arthritis. Our results imply that the
PADI4
haplotype associated with susceptibility to rheumatoid arthritis increases production of citrullinated peptides acting as autoantigens, resulting in heightened risk of developing the disease.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>12833157</pmid><doi>10.1038/ng1206</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2003-08, Vol.34 (4), p.395-402 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_73583636 |
| source | MEDLINE; Nature; Alma/SFX Local Collection |
| subjects | Adult Aged Aged, 80 and over Agriculture Animal Genetics and Genomics Antibodies Arthritis, Rheumatoid - enzymology Arthritis, Rheumatoid - genetics Arthritis, Rheumatoid - immunology Autoantibodies - blood Autoantigens - chemistry Autoantigens - metabolism Autoimmune diseases Biological and medical sciences Biomedical and Life Sciences Biomedicine Bone surgery Cancer Research Case-Control Studies Cell physiology Chemical research Chromosomes, Human, Pair 1 - genetics Citrulline - chemistry Citrulline - metabolism Diagnosis Disease Diseases of the osteoarticular system Enzymes Female Fundamental and applied biological sciences. Psychology Gene Function Genes Genetic aspects Genomes Haplotypes Hematology Hospitals Human Genetics Humans Hydrolases - genetics Hydrolases - metabolism Inflammatory joint diseases Intermediate Filament Proteins - chemistry Intermediate Filament Proteins - immunology Intermediate Filament Proteins - metabolism Linkage Disequilibrium Male Medical sciences Middle Aged Molecular and cellular biology Peptides Peptides - chemistry Peptides - immunology Peptides - metabolism Physiological aspects Polymorphism, Single Nucleotide Protein-Arginine Deiminases Rheumatoid arthritis Risk factors RNA Stability RNA, Messenger - genetics RNA, Messenger - metabolism Signal transduction Single nucleotide polymorphisms |
| title | Functional haplotypes of PADI4 , encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis |
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