HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk
HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk Analysis of the Type 1 Diabetes Genetics Consortium Families Henry Erlich 1 2 , Ana Maria Valdes 2 , Janelle Noble 2 , Joyce A. Carlson 3 , Mike Varney 4 , Pat Concannon 5 , Josyf C. Mychaleckyj 5 , John A. Todd 6 , Persia Bonella 2 , Anna...
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| creator | Erlich, Henry Valdes, Ana Maria Noble, Janelle Carlson, Joyce A. Varney, Mike Concannon, Pat Mychaleckyj, Josyf C. Todd, John A. Bonella, Persia Fear, Anna Lisa Lavant, Eva Louey, Anthony Moonsamy, Priscilla |
| description | HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk
Analysis of the Type 1 Diabetes Genetics Consortium Families
Henry Erlich 1 2 ,
Ana Maria Valdes 2 ,
Janelle Noble 2 ,
Joyce A. Carlson 3 ,
Mike Varney 4 ,
Pat Concannon 5 ,
Josyf C. Mychaleckyj 5 ,
John A. Todd 6 ,
Persia Bonella 2 ,
Anna Lisa Fear 2 ,
Eva Lavant 3 ,
Anthony Louey 4 ,
Priscilla Moonsamy 1 and
for the Type 1 Diabetes Genetics Consortium
1 Roche Molecular Systems, Alameda, California
2 Children's Hospital Oakland Research Institute, Oakland, California
3 Clinical Chemistry, University Hospital, Malmö, Sweden
4 Victorian Transplantation and Immunogenetics Service, Australian Red Cross Blood Service, Melbourne, Australia
5 Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia
6 Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics,
Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, U.K
Address correspondence and reprint requests to Henry A. Erlich, PhD, Roche Molecular Systems, 1145 Atlantic Ave., Alameda,
CA 94501. E-mail: Henry.Erlich{at}Roche.com
Abstract
OBJECTIVE— The Type 1 Diabetes Genetics Consortium has collected type 1 diabetic families worldwide for genetic analysis. The major genetic
determinants of type 1 diabetes are alleles at the HLA-DRB1 and DQB1 loci, with both susceptible and protective DR-DQ haplotypes
present in all human populations. The aim of this study is to estimate the risk conferred by specific DR-DQ haplotypes and
genotypes.
RESEARCH DESIGN AND METHODS:— Six hundred and seven Caucasian families and 38 Asian families were typed at high resolution for the DRB1, DQA1, and DQB1
loci. The association analysis was performed by comparing the frequency of DR-DQ haplotypes among the chromosomes transmitted
to an affected child with the frequency of chromosomes not transmitted to any affected child.
RESULTS— A number of susceptible, neutral, and protective DR-DQ haplotypes have been identified, and a statistically significant hierarchy
of type 1 diabetes risk has been established. The most susceptible haplotypes are the DRB1*0301-DQA1*0501-DQB1*0201 (odds
ratio [OR] 3.64) and the DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0401-DQA1*0301-DQB*0302, and DRB1*0402-DQA1*0301-DQB1*0302 haplotypes
(ORs 11.37, 8.39, and 3.63), followed by the DRB1*0404-DQA1*0301-DQB1*0302 (OR 1.59) and the DRB1*0801-DQB1*0401-DQB1*0402
( |
| doi_str_mv | 10.2337/db07-1331 |
| format | Article |
| fullrecord | <record><control><sourceid>highwire_cross</sourceid><recordid>TN_cdi_crossref_primary_10_2337_db07_1331</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>diabetes_57_4_1084</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2111-36c907122f7b51e7a4777018c97d5504cc48c9152ea69b39512df02fdaed2dda3</originalsourceid><addsrcrecordid>eNpNkNFLwzAQxoMobk4f_A_yKhLNJU2vwaex6ioUxDHBt5A2qavOrTQD2X9vygbKPdx3x3cfx4-Qa-B3Qkq8dxVHBlLCCRmDlppJge-nZMw5CAaocUQuQvjknKexzskIMqFEptWYPBTllOYLlr_Swnbr7W7f-UDtxtG53_ybllFRoHlrK7-Lu0Ubvi7JWWPXwV8d-4S8PT0uZwUrX-bPs2nJagEATKa15ghCNFgp8GgTROSQ1RqdUjyp6yRqUMLbVFdSKxCu4aJx1jvhnJUTcnPIrfttCL1vTNe337bfG-BmAGAGAGYAEL23B--q_Vj9tL037vjyn1BokniaJfIXXNJYOA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Erlich, Henry ; Valdes, Ana Maria ; Noble, Janelle ; Carlson, Joyce A. ; Varney, Mike ; Concannon, Pat ; Mychaleckyj, Josyf C. ; Todd, John A. ; Bonella, Persia ; Fear, Anna Lisa ; Lavant, Eva ; Louey, Anthony ; Moonsamy, Priscilla</creator><creatorcontrib>Erlich, Henry ; Valdes, Ana Maria ; Noble, Janelle ; Carlson, Joyce A. ; Varney, Mike ; Concannon, Pat ; Mychaleckyj, Josyf C. ; Todd, John A. ; Bonella, Persia ; Fear, Anna Lisa ; Lavant, Eva ; Louey, Anthony ; Moonsamy, Priscilla ; for the Type 1 Diabetes Genetics Consortium</creatorcontrib><description>HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk
Analysis of the Type 1 Diabetes Genetics Consortium Families
Henry Erlich 1 2 ,
Ana Maria Valdes 2 ,
Janelle Noble 2 ,
Joyce A. Carlson 3 ,
Mike Varney 4 ,
Pat Concannon 5 ,
Josyf C. Mychaleckyj 5 ,
John A. Todd 6 ,
Persia Bonella 2 ,
Anna Lisa Fear 2 ,
Eva Lavant 3 ,
Anthony Louey 4 ,
Priscilla Moonsamy 1 and
for the Type 1 Diabetes Genetics Consortium
1 Roche Molecular Systems, Alameda, California
2 Children's Hospital Oakland Research Institute, Oakland, California
3 Clinical Chemistry, University Hospital, Malmö, Sweden
4 Victorian Transplantation and Immunogenetics Service, Australian Red Cross Blood Service, Melbourne, Australia
5 Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia
6 Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics,
Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, U.K
Address correspondence and reprint requests to Henry A. Erlich, PhD, Roche Molecular Systems, 1145 Atlantic Ave., Alameda,
CA 94501. E-mail: Henry.Erlich{at}Roche.com
Abstract
OBJECTIVE— The Type 1 Diabetes Genetics Consortium has collected type 1 diabetic families worldwide for genetic analysis. The major genetic
determinants of type 1 diabetes are alleles at the HLA-DRB1 and DQB1 loci, with both susceptible and protective DR-DQ haplotypes
present in all human populations. The aim of this study is to estimate the risk conferred by specific DR-DQ haplotypes and
genotypes.
RESEARCH DESIGN AND METHODS:— Six hundred and seven Caucasian families and 38 Asian families were typed at high resolution for the DRB1, DQA1, and DQB1
loci. The association analysis was performed by comparing the frequency of DR-DQ haplotypes among the chromosomes transmitted
to an affected child with the frequency of chromosomes not transmitted to any affected child.
RESULTS— A number of susceptible, neutral, and protective DR-DQ haplotypes have been identified, and a statistically significant hierarchy
of type 1 diabetes risk has been established. The most susceptible haplotypes are the DRB1*0301-DQA1*0501-DQB1*0201 (odds
ratio [OR] 3.64) and the DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0401-DQA1*0301-DQB*0302, and DRB1*0402-DQA1*0301-DQB1*0302 haplotypes
(ORs 11.37, 8.39, and 3.63), followed by the DRB1*0404-DQA1*0301-DQB1*0302 (OR 1.59) and the DRB1*0801-DQB1*0401-DQB1*0402
(OR 1.25) haplotypes. The most protective haplotypes are DRB1*1501-DQA1*0102-DQB1*0602 (OR 0.03), DRB1*1401-DQA1*0101-DQB1*0503
(OR 0.02), and DRB1*0701-DQA1*0201-DQB1*0303 (OR 0.02).
CONCLUSIONS— Specific combinations of alleles at the DRB1, DQA1, and DQB1 loci determine the extent of haplotypic risk. The comparison
of closely related DR-DQ haplotype pairs with different type 1 diabetes risks allowed identification of specific amino acid
positions critical in determining disease susceptibility. These data also indicate that the risk associated with specific
HLA haplotypes can be influenced by the genotype context and that the trans- complementing heterodimer encoded by DQA1*0501 and DQB1*0302 confers very high risk.
AFBAC, affected family-based control
SNP, single nucleotide polymorphism
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 5 February 2008. DOI: 10.2337/db07-1331.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-1331 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted January 14, 2008.
Received September 18, 2007.
DIABETES</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db07-1331</identifier><identifier>PMID: 18252895</identifier><language>eng</language><publisher>American Diabetes Association</publisher><ispartof>Diabetes (New York, N.Y.), 2008-04, Vol.57 (4), p.1084-1092</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2111-36c907122f7b51e7a4777018c97d5504cc48c9152ea69b39512df02fdaed2dda3</citedby><cites>FETCH-LOGICAL-c2111-36c907122f7b51e7a4777018c97d5504cc48c9152ea69b39512df02fdaed2dda3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27911,27912</link.rule.ids></links><search><creatorcontrib>Erlich, Henry</creatorcontrib><creatorcontrib>Valdes, Ana Maria</creatorcontrib><creatorcontrib>Noble, Janelle</creatorcontrib><creatorcontrib>Carlson, Joyce A.</creatorcontrib><creatorcontrib>Varney, Mike</creatorcontrib><creatorcontrib>Concannon, Pat</creatorcontrib><creatorcontrib>Mychaleckyj, Josyf C.</creatorcontrib><creatorcontrib>Todd, John A.</creatorcontrib><creatorcontrib>Bonella, Persia</creatorcontrib><creatorcontrib>Fear, Anna Lisa</creatorcontrib><creatorcontrib>Lavant, Eva</creatorcontrib><creatorcontrib>Louey, Anthony</creatorcontrib><creatorcontrib>Moonsamy, Priscilla</creatorcontrib><creatorcontrib>for the Type 1 Diabetes Genetics Consortium</creatorcontrib><title>HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk</title><title>Diabetes (New York, N.Y.)</title><description>HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk
Analysis of the Type 1 Diabetes Genetics Consortium Families
Henry Erlich 1 2 ,
Ana Maria Valdes 2 ,
Janelle Noble 2 ,
Joyce A. Carlson 3 ,
Mike Varney 4 ,
Pat Concannon 5 ,
Josyf C. Mychaleckyj 5 ,
John A. Todd 6 ,
Persia Bonella 2 ,
Anna Lisa Fear 2 ,
Eva Lavant 3 ,
Anthony Louey 4 ,
Priscilla Moonsamy 1 and
for the Type 1 Diabetes Genetics Consortium
1 Roche Molecular Systems, Alameda, California
2 Children's Hospital Oakland Research Institute, Oakland, California
3 Clinical Chemistry, University Hospital, Malmö, Sweden
4 Victorian Transplantation and Immunogenetics Service, Australian Red Cross Blood Service, Melbourne, Australia
5 Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia
6 Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics,
Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, U.K
Address correspondence and reprint requests to Henry A. Erlich, PhD, Roche Molecular Systems, 1145 Atlantic Ave., Alameda,
CA 94501. E-mail: Henry.Erlich{at}Roche.com
Abstract
OBJECTIVE— The Type 1 Diabetes Genetics Consortium has collected type 1 diabetic families worldwide for genetic analysis. The major genetic
determinants of type 1 diabetes are alleles at the HLA-DRB1 and DQB1 loci, with both susceptible and protective DR-DQ haplotypes
present in all human populations. The aim of this study is to estimate the risk conferred by specific DR-DQ haplotypes and
genotypes.
RESEARCH DESIGN AND METHODS:— Six hundred and seven Caucasian families and 38 Asian families were typed at high resolution for the DRB1, DQA1, and DQB1
loci. The association analysis was performed by comparing the frequency of DR-DQ haplotypes among the chromosomes transmitted
to an affected child with the frequency of chromosomes not transmitted to any affected child.
RESULTS— A number of susceptible, neutral, and protective DR-DQ haplotypes have been identified, and a statistically significant hierarchy
of type 1 diabetes risk has been established. The most susceptible haplotypes are the DRB1*0301-DQA1*0501-DQB1*0201 (odds
ratio [OR] 3.64) and the DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0401-DQA1*0301-DQB*0302, and DRB1*0402-DQA1*0301-DQB1*0302 haplotypes
(ORs 11.37, 8.39, and 3.63), followed by the DRB1*0404-DQA1*0301-DQB1*0302 (OR 1.59) and the DRB1*0801-DQB1*0401-DQB1*0402
(OR 1.25) haplotypes. The most protective haplotypes are DRB1*1501-DQA1*0102-DQB1*0602 (OR 0.03), DRB1*1401-DQA1*0101-DQB1*0503
(OR 0.02), and DRB1*0701-DQA1*0201-DQB1*0303 (OR 0.02).
CONCLUSIONS— Specific combinations of alleles at the DRB1, DQA1, and DQB1 loci determine the extent of haplotypic risk. The comparison
of closely related DR-DQ haplotype pairs with different type 1 diabetes risks allowed identification of specific amino acid
positions critical in determining disease susceptibility. These data also indicate that the risk associated with specific
HLA haplotypes can be influenced by the genotype context and that the trans- complementing heterodimer encoded by DQA1*0501 and DQB1*0302 confers very high risk.
AFBAC, affected family-based control
SNP, single nucleotide polymorphism
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 5 February 2008. DOI: 10.2337/db07-1331.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-1331 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted January 14, 2008.
Received September 18, 2007.
DIABETES</description><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNpNkNFLwzAQxoMobk4f_A_yKhLNJU2vwaex6ioUxDHBt5A2qavOrTQD2X9vygbKPdx3x3cfx4-Qa-B3Qkq8dxVHBlLCCRmDlppJge-nZMw5CAaocUQuQvjknKexzskIMqFEptWYPBTllOYLlr_Swnbr7W7f-UDtxtG53_ybllFRoHlrK7-Lu0Ubvi7JWWPXwV8d-4S8PT0uZwUrX-bPs2nJagEATKa15ghCNFgp8GgTROSQ1RqdUjyp6yRqUMLbVFdSKxCu4aJx1jvhnJUTcnPIrfttCL1vTNe337bfG-BmAGAGAGYAEL23B--q_Vj9tL037vjyn1BokniaJfIXXNJYOA</recordid><startdate>20080401</startdate><enddate>20080401</enddate><creator>Erlich, Henry</creator><creator>Valdes, Ana Maria</creator><creator>Noble, Janelle</creator><creator>Carlson, Joyce A.</creator><creator>Varney, Mike</creator><creator>Concannon, Pat</creator><creator>Mychaleckyj, Josyf C.</creator><creator>Todd, John A.</creator><creator>Bonella, Persia</creator><creator>Fear, Anna Lisa</creator><creator>Lavant, Eva</creator><creator>Louey, Anthony</creator><creator>Moonsamy, Priscilla</creator><general>American Diabetes Association</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20080401</creationdate><title>HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk</title><author>Erlich, Henry ; Valdes, Ana Maria ; Noble, Janelle ; Carlson, Joyce A. ; Varney, Mike ; Concannon, Pat ; Mychaleckyj, Josyf C. ; Todd, John A. ; Bonella, Persia ; Fear, Anna Lisa ; Lavant, Eva ; Louey, Anthony ; Moonsamy, Priscilla</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2111-36c907122f7b51e7a4777018c97d5504cc48c9152ea69b39512df02fdaed2dda3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Erlich, Henry</creatorcontrib><creatorcontrib>Valdes, Ana Maria</creatorcontrib><creatorcontrib>Noble, Janelle</creatorcontrib><creatorcontrib>Carlson, Joyce A.</creatorcontrib><creatorcontrib>Varney, Mike</creatorcontrib><creatorcontrib>Concannon, Pat</creatorcontrib><creatorcontrib>Mychaleckyj, Josyf C.</creatorcontrib><creatorcontrib>Todd, John A.</creatorcontrib><creatorcontrib>Bonella, Persia</creatorcontrib><creatorcontrib>Fear, Anna Lisa</creatorcontrib><creatorcontrib>Lavant, Eva</creatorcontrib><creatorcontrib>Louey, Anthony</creatorcontrib><creatorcontrib>Moonsamy, Priscilla</creatorcontrib><creatorcontrib>for the Type 1 Diabetes Genetics Consortium</creatorcontrib><collection>CrossRef</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Erlich, Henry</au><au>Valdes, Ana Maria</au><au>Noble, Janelle</au><au>Carlson, Joyce A.</au><au>Varney, Mike</au><au>Concannon, Pat</au><au>Mychaleckyj, Josyf C.</au><au>Todd, John A.</au><au>Bonella, Persia</au><au>Fear, Anna Lisa</au><au>Lavant, Eva</au><au>Louey, Anthony</au><au>Moonsamy, Priscilla</au><aucorp>for the Type 1 Diabetes Genetics Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><date>2008-04-01</date><risdate>2008</risdate><volume>57</volume><issue>4</issue><spage>1084</spage><epage>1092</epage><pages>1084-1092</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><abstract>HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk
Analysis of the Type 1 Diabetes Genetics Consortium Families
Henry Erlich 1 2 ,
Ana Maria Valdes 2 ,
Janelle Noble 2 ,
Joyce A. Carlson 3 ,
Mike Varney 4 ,
Pat Concannon 5 ,
Josyf C. Mychaleckyj 5 ,
John A. Todd 6 ,
Persia Bonella 2 ,
Anna Lisa Fear 2 ,
Eva Lavant 3 ,
Anthony Louey 4 ,
Priscilla Moonsamy 1 and
for the Type 1 Diabetes Genetics Consortium
1 Roche Molecular Systems, Alameda, California
2 Children's Hospital Oakland Research Institute, Oakland, California
3 Clinical Chemistry, University Hospital, Malmö, Sweden
4 Victorian Transplantation and Immunogenetics Service, Australian Red Cross Blood Service, Melbourne, Australia
5 Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia
6 Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics,
Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, U.K
Address correspondence and reprint requests to Henry A. Erlich, PhD, Roche Molecular Systems, 1145 Atlantic Ave., Alameda,
CA 94501. E-mail: Henry.Erlich{at}Roche.com
Abstract
OBJECTIVE— The Type 1 Diabetes Genetics Consortium has collected type 1 diabetic families worldwide for genetic analysis. The major genetic
determinants of type 1 diabetes are alleles at the HLA-DRB1 and DQB1 loci, with both susceptible and protective DR-DQ haplotypes
present in all human populations. The aim of this study is to estimate the risk conferred by specific DR-DQ haplotypes and
genotypes.
RESEARCH DESIGN AND METHODS:— Six hundred and seven Caucasian families and 38 Asian families were typed at high resolution for the DRB1, DQA1, and DQB1
loci. The association analysis was performed by comparing the frequency of DR-DQ haplotypes among the chromosomes transmitted
to an affected child with the frequency of chromosomes not transmitted to any affected child.
RESULTS— A number of susceptible, neutral, and protective DR-DQ haplotypes have been identified, and a statistically significant hierarchy
of type 1 diabetes risk has been established. The most susceptible haplotypes are the DRB1*0301-DQA1*0501-DQB1*0201 (odds
ratio [OR] 3.64) and the DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0401-DQA1*0301-DQB*0302, and DRB1*0402-DQA1*0301-DQB1*0302 haplotypes
(ORs 11.37, 8.39, and 3.63), followed by the DRB1*0404-DQA1*0301-DQB1*0302 (OR 1.59) and the DRB1*0801-DQB1*0401-DQB1*0402
(OR 1.25) haplotypes. The most protective haplotypes are DRB1*1501-DQA1*0102-DQB1*0602 (OR 0.03), DRB1*1401-DQA1*0101-DQB1*0503
(OR 0.02), and DRB1*0701-DQA1*0201-DQB1*0303 (OR 0.02).
CONCLUSIONS— Specific combinations of alleles at the DRB1, DQA1, and DQB1 loci determine the extent of haplotypic risk. The comparison
of closely related DR-DQ haplotype pairs with different type 1 diabetes risks allowed identification of specific amino acid
positions critical in determining disease susceptibility. These data also indicate that the risk associated with specific
HLA haplotypes can be influenced by the genotype context and that the trans- complementing heterodimer encoded by DQA1*0501 and DQB1*0302 confers very high risk.
AFBAC, affected family-based control
SNP, single nucleotide polymorphism
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 5 February 2008. DOI: 10.2337/db07-1331.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-1331 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted January 14, 2008.
Received September 18, 2007.
DIABETES</abstract><pub>American Diabetes Association</pub><pmid>18252895</pmid><doi>10.2337/db07-1331</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| title | HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk |
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