Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians
Objective To define the relative importance (RI) of class II major histocompatibility complex (MHC) alleles and peptide binding motifs as risk or protective factors for juvenile dermatomyositis (DM), and to compare these with HLA associations in adult DM. Methods DRB1 and DQA1 typing was performed i...
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| Veröffentlicht in: | Arthritis and rheumatism 2006-12, Vol.54 (12), p.3979-3987 |
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| creator | Mamyrova, Gulnara O'Hanlon, Terrance P. Monroe, Jason B. Carrick, Danielle Mercatante Malley, James D. Adams, Sharon Reed, Ann M. Shamim, Ejaz A. James‐Newton, Laura Miller, Frederick W. Rider, Lisa G. |
| description | Objective
To define the relative importance (RI) of class II major histocompatibility complex (MHC) alleles and peptide binding motifs as risk or protective factors for juvenile dermatomyositis (DM), and to compare these with HLA associations in adult DM.
Methods
DRB1 and DQA1 typing was performed in 142 Caucasian patients with juvenile DM, and the results were compared with HLA typing data from 193 patients with adult DM and 797 race‐matched controls. Random Forests classification and multiple logistic regression were used to assess the RI of the HLA associations.
Results
The HLA–DRB1*0301 allele was a primary risk factor (odds ratio [OR] 3.9), while DQA1*0301 (OR 2.8), DQA1*0501 (OR 2.1), and homozygosity for DQA1*0501 (OR 3.2) were additional risk factors for juvenile DM. These risk factors were not present in patients with adult DM without defined autoantibodies. DQA1 alleles *0201 (OR 0.37), *0101 (OR 0.38), and *0102 (OR 0.51) were identified as novel protective factors for juvenile DM, the latter 2 also being protective factors in adult DM. The peptide binding motif DRB1 9EYSTS13 was a risk factor, and DQA1 motifs F25, S26, and 45(V/A)W(R/K)47 were protective. Random Forests classification analysis revealed that among the identified risk factors for juvenile DM, DRB1*0301 had a higher RI (100%) than DQA1*0301 (RI 57%), DQA1*0501 (RI 42%), or the peptide binding motifs. In a logistic regression model, DRB1*0301 and DQA1*0201 were the strongest risk and protective factors, respectively, for juvenile DM.
Conclusion
DRB1*0301 is ranked higher in RI than DQA1*0501 as a risk factor for juvenile DM. DQA1*0301 is a newly identified HLA risk factor for juvenile DM, while 3 of the DQA1 alleles studied are newly identified protective factors for juvenile DM. |
| doi_str_mv | 10.1002/art.22216 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2063456</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20835956</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5406-be0aef01823ff9f6e254cf5312a1c4cee9fae560450a15cded9db3a8a12ea7f43</originalsourceid><addsrcrecordid>eNqFkU1rGzEQhkVpaZykh_6BoksDOWyij9V691IIJkkDgUJxzmKsHaVKdyVX0jr430eNTdIeSk_DMA_vDPMQ8pGzM86YOIeYz4QQvHlDZlyJrmJc8rdkxhirK6k6fkAOU3oorZBKvicHfM6lbLiYkeXNOE4-3KPH7AyNLv2k4Hu6jiGjyW6D1ILJISZqQ6QP0wa9G5D2GEfIYdyG5LJL1Hm6gMlAcuDTMXlnYUj4YV-PyN3V5XLxtbr9dn2zuLitjKpZU62QAVrGWyGt7WyDQtXGKskFcFMbxM4CqobVigFXpse-61cSWuACYW5reUS-7HLX02rE3qDPEQa9jm6EuNUBnP574t0PfR82WrBG1qopASf7gBh-TZiyHl0yOAzgMUxJN62Yz5nq_gsK1pY_Pyee7kATQ0oR7cs1nOnfsnSRpZ9lFfbTn-e_kns7Bfi8ByAZGGwEb1x65VpZt-VdhTvfcY9FzfbfG_XF9-Vu9ROfe65z</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20835956</pqid></control><display><type>article</type><title>Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Mamyrova, Gulnara ; O'Hanlon, Terrance P. ; Monroe, Jason B. ; Carrick, Danielle Mercatante ; Malley, James D. ; Adams, Sharon ; Reed, Ann M. ; Shamim, Ejaz A. ; James‐Newton, Laura ; Miller, Frederick W. ; Rider, Lisa G.</creator><creatorcontrib>Mamyrova, Gulnara ; O'Hanlon, Terrance P. ; Monroe, Jason B. ; Carrick, Danielle Mercatante ; Malley, James D. ; Adams, Sharon ; Reed, Ann M. ; Shamim, Ejaz A. ; James‐Newton, Laura ; Miller, Frederick W. ; Rider, Lisa G. ; Childhood Myositis Heterogeneity Collaborative Study Group</creatorcontrib><description>Objective
To define the relative importance (RI) of class II major histocompatibility complex (MHC) alleles and peptide binding motifs as risk or protective factors for juvenile dermatomyositis (DM), and to compare these with HLA associations in adult DM.
Methods
DRB1 and DQA1 typing was performed in 142 Caucasian patients with juvenile DM, and the results were compared with HLA typing data from 193 patients with adult DM and 797 race‐matched controls. Random Forests classification and multiple logistic regression were used to assess the RI of the HLA associations.
Results
The HLA–DRB1*0301 allele was a primary risk factor (odds ratio [OR] 3.9), while DQA1*0301 (OR 2.8), DQA1*0501 (OR 2.1), and homozygosity for DQA1*0501 (OR 3.2) were additional risk factors for juvenile DM. These risk factors were not present in patients with adult DM without defined autoantibodies. DQA1 alleles *0201 (OR 0.37), *0101 (OR 0.38), and *0102 (OR 0.51) were identified as novel protective factors for juvenile DM, the latter 2 also being protective factors in adult DM. The peptide binding motif DRB1 9EYSTS13 was a risk factor, and DQA1 motifs F25, S26, and 45(V/A)W(R/K)47 were protective. Random Forests classification analysis revealed that among the identified risk factors for juvenile DM, DRB1*0301 had a higher RI (100%) than DQA1*0301 (RI 57%), DQA1*0501 (RI 42%), or the peptide binding motifs. In a logistic regression model, DRB1*0301 and DQA1*0201 were the strongest risk and protective factors, respectively, for juvenile DM.
Conclusion
DRB1*0301 is ranked higher in RI than DQA1*0501 as a risk factor for juvenile DM. DQA1*0301 is a newly identified HLA risk factor for juvenile DM, while 3 of the DQA1 alleles studied are newly identified protective factors for juvenile DM.</description><identifier>ISSN: 0004-3591</identifier><identifier>EISSN: 1529-0131</identifier><identifier>DOI: 10.1002/art.22216</identifier><identifier>PMID: 17133612</identifier><identifier>CODEN: ARHEAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adolescent ; Adult ; Binding Sites ; Biological and medical sciences ; Dermatomyositis - diagnosis ; Dermatomyositis - genetics ; Dermatomyositis - immunology ; European Continental Ancestry Group - genetics ; Genetic Predisposition to Disease ; Histocompatibility Testing ; HLA-DQ alpha-Chains ; HLA-DQ Antigens - genetics ; HLA-DQ Antigens - immunology ; HLA-DR Antigens - genetics ; HLA-DR Antigens - immunology ; HLA-DRB1 Chains ; Humans ; Medical sciences ; Odds Ratio ; Risk Factors ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</subject><ispartof>Arthritis and rheumatism, 2006-12, Vol.54 (12), p.3979-3987</ispartof><rights>Copyright © 2006 by the American College of Rheumatology</rights><rights>2007 INIST-CNRS</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5406-be0aef01823ff9f6e254cf5312a1c4cee9fae560450a15cded9db3a8a12ea7f43</citedby><cites>FETCH-LOGICAL-c5406-be0aef01823ff9f6e254cf5312a1c4cee9fae560450a15cded9db3a8a12ea7f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fart.22216$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fart.22216$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18348531$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17133612$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mamyrova, Gulnara</creatorcontrib><creatorcontrib>O'Hanlon, Terrance P.</creatorcontrib><creatorcontrib>Monroe, Jason B.</creatorcontrib><creatorcontrib>Carrick, Danielle Mercatante</creatorcontrib><creatorcontrib>Malley, James D.</creatorcontrib><creatorcontrib>Adams, Sharon</creatorcontrib><creatorcontrib>Reed, Ann M.</creatorcontrib><creatorcontrib>Shamim, Ejaz A.</creatorcontrib><creatorcontrib>James‐Newton, Laura</creatorcontrib><creatorcontrib>Miller, Frederick W.</creatorcontrib><creatorcontrib>Rider, Lisa G.</creatorcontrib><creatorcontrib>Childhood Myositis Heterogeneity Collaborative Study Group</creatorcontrib><title>Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians</title><title>Arthritis and rheumatism</title><addtitle>Arthritis Rheum</addtitle><description>Objective
To define the relative importance (RI) of class II major histocompatibility complex (MHC) alleles and peptide binding motifs as risk or protective factors for juvenile dermatomyositis (DM), and to compare these with HLA associations in adult DM.
Methods
DRB1 and DQA1 typing was performed in 142 Caucasian patients with juvenile DM, and the results were compared with HLA typing data from 193 patients with adult DM and 797 race‐matched controls. Random Forests classification and multiple logistic regression were used to assess the RI of the HLA associations.
Results
The HLA–DRB1*0301 allele was a primary risk factor (odds ratio [OR] 3.9), while DQA1*0301 (OR 2.8), DQA1*0501 (OR 2.1), and homozygosity for DQA1*0501 (OR 3.2) were additional risk factors for juvenile DM. These risk factors were not present in patients with adult DM without defined autoantibodies. DQA1 alleles *0201 (OR 0.37), *0101 (OR 0.38), and *0102 (OR 0.51) were identified as novel protective factors for juvenile DM, the latter 2 also being protective factors in adult DM. The peptide binding motif DRB1 9EYSTS13 was a risk factor, and DQA1 motifs F25, S26, and 45(V/A)W(R/K)47 were protective. Random Forests classification analysis revealed that among the identified risk factors for juvenile DM, DRB1*0301 had a higher RI (100%) than DQA1*0301 (RI 57%), DQA1*0501 (RI 42%), or the peptide binding motifs. In a logistic regression model, DRB1*0301 and DQA1*0201 were the strongest risk and protective factors, respectively, for juvenile DM.
Conclusion
DRB1*0301 is ranked higher in RI than DQA1*0501 as a risk factor for juvenile DM. DQA1*0301 is a newly identified HLA risk factor for juvenile DM, while 3 of the DQA1 alleles studied are newly identified protective factors for juvenile DM.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Dermatomyositis - diagnosis</subject><subject>Dermatomyositis - genetics</subject><subject>Dermatomyositis - immunology</subject><subject>European Continental Ancestry Group - genetics</subject><subject>Genetic Predisposition to Disease</subject><subject>Histocompatibility Testing</subject><subject>HLA-DQ alpha-Chains</subject><subject>HLA-DQ Antigens - genetics</subject><subject>HLA-DQ Antigens - immunology</subject><subject>HLA-DR Antigens - genetics</subject><subject>HLA-DR Antigens - immunology</subject><subject>HLA-DRB1 Chains</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Odds Ratio</subject><subject>Risk Factors</subject><subject>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</subject><issn>0004-3591</issn><issn>1529-0131</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1rGzEQhkVpaZykh_6BoksDOWyij9V691IIJkkDgUJxzmKsHaVKdyVX0jr430eNTdIeSk_DMA_vDPMQ8pGzM86YOIeYz4QQvHlDZlyJrmJc8rdkxhirK6k6fkAOU3oorZBKvicHfM6lbLiYkeXNOE4-3KPH7AyNLv2k4Hu6jiGjyW6D1ILJISZqQ6QP0wa9G5D2GEfIYdyG5LJL1Hm6gMlAcuDTMXlnYUj4YV-PyN3V5XLxtbr9dn2zuLitjKpZU62QAVrGWyGt7WyDQtXGKskFcFMbxM4CqobVigFXpse-61cSWuACYW5reUS-7HLX02rE3qDPEQa9jm6EuNUBnP574t0PfR82WrBG1qopASf7gBh-TZiyHl0yOAzgMUxJN62Yz5nq_gsK1pY_Pyee7kATQ0oR7cs1nOnfsnSRpZ9lFfbTn-e_kns7Bfi8ByAZGGwEb1x65VpZt-VdhTvfcY9FzfbfG_XF9-Vu9ROfe65z</recordid><startdate>200612</startdate><enddate>200612</enddate><creator>Mamyrova, Gulnara</creator><creator>O'Hanlon, Terrance P.</creator><creator>Monroe, Jason B.</creator><creator>Carrick, Danielle Mercatante</creator><creator>Malley, James D.</creator><creator>Adams, Sharon</creator><creator>Reed, Ann M.</creator><creator>Shamim, Ejaz A.</creator><creator>James‐Newton, Laura</creator><creator>Miller, Frederick W.</creator><creator>Rider, Lisa G.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</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>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200612</creationdate><title>Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians</title><author>Mamyrova, Gulnara ; O'Hanlon, Terrance P. ; Monroe, Jason B. ; Carrick, Danielle Mercatante ; Malley, James D. ; Adams, Sharon ; Reed, Ann M. ; Shamim, Ejaz A. ; James‐Newton, Laura ; Miller, Frederick W. ; Rider, Lisa G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5406-be0aef01823ff9f6e254cf5312a1c4cee9fae560450a15cded9db3a8a12ea7f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Dermatomyositis - diagnosis</topic><topic>Dermatomyositis - genetics</topic><topic>Dermatomyositis - immunology</topic><topic>European Continental Ancestry Group - genetics</topic><topic>Genetic Predisposition to Disease</topic><topic>Histocompatibility Testing</topic><topic>HLA-DQ alpha-Chains</topic><topic>HLA-DQ Antigens - genetics</topic><topic>HLA-DQ Antigens - immunology</topic><topic>HLA-DR Antigens - genetics</topic><topic>HLA-DR Antigens - immunology</topic><topic>HLA-DRB1 Chains</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Odds Ratio</topic><topic>Risk Factors</topic><topic>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</topic><toplevel>online_resources</toplevel><creatorcontrib>Mamyrova, Gulnara</creatorcontrib><creatorcontrib>O'Hanlon, Terrance P.</creatorcontrib><creatorcontrib>Monroe, Jason B.</creatorcontrib><creatorcontrib>Carrick, Danielle Mercatante</creatorcontrib><creatorcontrib>Malley, James D.</creatorcontrib><creatorcontrib>Adams, Sharon</creatorcontrib><creatorcontrib>Reed, Ann M.</creatorcontrib><creatorcontrib>Shamim, Ejaz A.</creatorcontrib><creatorcontrib>James‐Newton, Laura</creatorcontrib><creatorcontrib>Miller, Frederick W.</creatorcontrib><creatorcontrib>Rider, Lisa G.</creatorcontrib><creatorcontrib>Childhood Myositis Heterogeneity Collaborative Study Group</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>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Arthritis and rheumatism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mamyrova, Gulnara</au><au>O'Hanlon, Terrance P.</au><au>Monroe, Jason B.</au><au>Carrick, Danielle Mercatante</au><au>Malley, James D.</au><au>Adams, Sharon</au><au>Reed, Ann M.</au><au>Shamim, Ejaz A.</au><au>James‐Newton, Laura</au><au>Miller, Frederick W.</au><au>Rider, Lisa G.</au><aucorp>Childhood Myositis Heterogeneity Collaborative Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians</atitle><jtitle>Arthritis and rheumatism</jtitle><addtitle>Arthritis Rheum</addtitle><date>2006-12</date><risdate>2006</risdate><volume>54</volume><issue>12</issue><spage>3979</spage><epage>3987</epage><pages>3979-3987</pages><issn>0004-3591</issn><eissn>1529-0131</eissn><coden>ARHEAW</coden><abstract>Objective
To define the relative importance (RI) of class II major histocompatibility complex (MHC) alleles and peptide binding motifs as risk or protective factors for juvenile dermatomyositis (DM), and to compare these with HLA associations in adult DM.
Methods
DRB1 and DQA1 typing was performed in 142 Caucasian patients with juvenile DM, and the results were compared with HLA typing data from 193 patients with adult DM and 797 race‐matched controls. Random Forests classification and multiple logistic regression were used to assess the RI of the HLA associations.
Results
The HLA–DRB1*0301 allele was a primary risk factor (odds ratio [OR] 3.9), while DQA1*0301 (OR 2.8), DQA1*0501 (OR 2.1), and homozygosity for DQA1*0501 (OR 3.2) were additional risk factors for juvenile DM. These risk factors were not present in patients with adult DM without defined autoantibodies. DQA1 alleles *0201 (OR 0.37), *0101 (OR 0.38), and *0102 (OR 0.51) were identified as novel protective factors for juvenile DM, the latter 2 also being protective factors in adult DM. The peptide binding motif DRB1 9EYSTS13 was a risk factor, and DQA1 motifs F25, S26, and 45(V/A)W(R/K)47 were protective. Random Forests classification analysis revealed that among the identified risk factors for juvenile DM, DRB1*0301 had a higher RI (100%) than DQA1*0301 (RI 57%), DQA1*0501 (RI 42%), or the peptide binding motifs. In a logistic regression model, DRB1*0301 and DQA1*0201 were the strongest risk and protective factors, respectively, for juvenile DM.
Conclusion
DRB1*0301 is ranked higher in RI than DQA1*0501 as a risk factor for juvenile DM. DQA1*0301 is a newly identified HLA risk factor for juvenile DM, while 3 of the DQA1 alleles studied are newly identified protective factors for juvenile DM.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>17133612</pmid><doi>10.1002/art.22216</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Arthritis and rheumatism, 2006-12, Vol.54 (12), p.3979-3987 |
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| subjects | Adolescent Adult Binding Sites Biological and medical sciences Dermatomyositis - diagnosis Dermatomyositis - genetics Dermatomyositis - immunology European Continental Ancestry Group - genetics Genetic Predisposition to Disease Histocompatibility Testing HLA-DQ alpha-Chains HLA-DQ Antigens - genetics HLA-DQ Antigens - immunology HLA-DR Antigens - genetics HLA-DR Antigens - immunology HLA-DRB1 Chains Humans Medical sciences Odds Ratio Risk Factors Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis |
| title | Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians |
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