HLA Class II ( DR , DQ, DP ) Genes Were Separately Associated With the Progression From Seroconversion to Onset of Type 1 Diabetes Among Participants in Two Diabetes Prevention Trials (DPT-1 and TN07)

To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D). Next-generation targeted sequencing was used to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants f...

Full description

Saved in:
Bibliographic Details
Published inDiabetes care Vol. 47; no. 5; pp. 826 - 834
Main Authors Zhao, Lue Ping, Papadopoulos, George K., Skyler, Jay S., Pugliese, Alberto, Parikh, Hemang M., Kwok, William W., Lybrand, Terry P., Bondinas, George P., Moustakas, Antonis K., Wang, Ruihan, Pyo, Chul-Woo, Nelson, Wyatt C., Geraghty, Daniel E., Lernmark, Åke
Format Journal Article
LanguageEnglish
Published United States American Diabetes Association 01.05.2024
Subjects
Alleles
Autoantibodies
Autoimmunity
Clinical Medicine
Clinical trials
Diabetes
Diabetes mellitus (insulin dependent)
Diabetes Mellitus, Type 1 - genetics
Diabetes Mellitus, Type 1 - prevention & control
Disease prevention
Disease Progression
DQA1 protein
Drb1 protein
Endocrinology and Diabetes
Endokrinologi och diabetes
Gene Frequency
Genes
Genotype
Haplotypes
Histocompatibility antigen HLA
HLA-DQ beta-Chains - genetics
HLA-DRB1 Chains - genetics
Humans
Immunogenicity
Klinisk medicin
Linkage disequilibrium
Medical and Health Sciences
Medicin och hälsovetenskap
Original
Pathogenesis
Regression models
Research design
Seroconversion
Online AccessGet full text

Cover

Abstract To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D). Next-generation targeted sequencing was used to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants from the Diabetes Prevention Trial-1 and Randomized Diabetes Prevention Trial with Oral Insulin sponsored by TrialNet. By the linkage disequilibrium, DQA1 and DQB1 are haplotyped to form DQ haplotypes; DP and DR haplotypes are similarly constructed. Together with available clinical covariables, we applied the Cox regression model to assess HLAII immunogenic associations with the disease progression. First, the current investigation updated the previously reported genetic associations of DQA1*03:01-DQB1*03:02 (hazard ratio [HR] = 1.25, P = 3.50*10-3) and DQA1*03:03-DQB1*03:01 (HR = 0.56, P = 1.16*10-3), and also uncovered a risk association with DQA1*05:01-DQB1*02:01 (HR = 1.19, P = 0.041). Second, after adjusting for DQ, DPA1*02:01-DPB1*11:01 and DPA1*01:03-DPB1*03:01 were found to have opposite associations with progression (HR = 1.98 and 0.70, P = 0.021 and 6.16*10-3, respectively). Third, DRB1*03:01-DRB3*01:01 and DRB1*03:01-DRB3*02:02, sharing the DRB1*03:01, had opposite associations (HR = 0.73 and 1.44, P = 0.04 and 0.019, respectively), indicating a role of DRB3. Meanwhile, DRB1*12:01-DRB3*02:02 and DRB1*01:03 alone were found to associate with progression (HR = 2.6 and 2.32, P = 0.018 and 0.039, respectively). Fourth, through enumerating all heterodimers, it was found that both DQ and DP could exhibit associations with disease progression. These results suggest that HLAII polymorphisms influence progression from islet autoimmunity to T1D among at-risk subjects with islet autoantibodies.
AbstractList OBJECTIVE: To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: Next-generation targeted sequencing was used to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants from the Diabetes Prevention Trial-1 and Randomized Diabetes Prevention Trial with Oral Insulin sponsored by TrialNet. By the linkage disequilibrium, DQA1 and DQB1 are haplotyped to form DQ haplotypes; DP and DR haplotypes are similarly constructed. Together with available clinical covariables, we applied the Cox regression model to assess HLAII immunogenic associations with the disease progression.RESULTS: 1) The current investigation updated the previously reported genetic associations of DQA1*03:01-DQB1*03:02 (hazard ratio [HR] = 1.25, P = 3.50*10-3) and DQA1*03:03-DQB1*03:01 (HR = 0.56, P = 1.16*10-3), and also uncovered a risk association with DQA1*05:01-DQB1*02:01 (HR = 1.19, P = 0.041). 2) After adjusting for DQ, DPA1*02:01-DPB1*11:01 and DPA1*01:03-DPB1*03:01 were found to have opposite associations with progression (HR = 1.98 and 0.70, P = 0.021 and 6.16*10-3, respectively). 3) DRB1*03:01-DRB3*01:01 and DRB1*03:01-DRB3*02:02, sharing the DRB1*03:01, had opposite associations (HR = 0.73 and 1.44, P = 0.04 and 0.019, respectively), indicating a role of DRB3. Meanwhile, DRB1*12:01-DRB3*02:02 and DRB1*01:03 alone were found to associate with progression (HR = 2.6 and 2.32, P = 0.018 and 0.039, respectively). 4) Through enumerating all heterodimers, it was found that both DQ and DP could exhibit associations with disease progression.CONCLUSIONS: These results suggest that HLAII polymorphisms influence progression from islet autoimmunity to T1D among at-risk subjects with islet autoantibodies.
To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D).OBJECTIVETo explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D).Next-generation targeted sequencing was used to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants from the Diabetes Prevention Trial-1 and Randomized Diabetes Prevention Trial with Oral Insulin sponsored by TrialNet. By the linkage disequilibrium, DQA1 and DQB1 are haplotyped to form DQ haplotypes; DP and DR haplotypes are similarly constructed. Together with available clinical covariables, we applied the Cox regression model to assess HLAII immunogenic associations with the disease progression.RESEARCH DESIGN AND METHODSNext-generation targeted sequencing was used to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants from the Diabetes Prevention Trial-1 and Randomized Diabetes Prevention Trial with Oral Insulin sponsored by TrialNet. By the linkage disequilibrium, DQA1 and DQB1 are haplotyped to form DQ haplotypes; DP and DR haplotypes are similarly constructed. Together with available clinical covariables, we applied the Cox regression model to assess HLAII immunogenic associations with the disease progression.First, the current investigation updated the previously reported genetic associations of DQA1*03:01-DQB1*03:02 (hazard ratio [HR] = 1.25, P = 3.50*10-3) and DQA1*03:03-DQB1*03:01 (HR = 0.56, P = 1.16*10-3), and also uncovered a risk association with DQA1*05:01-DQB1*02:01 (HR = 1.19, P = 0.041). Second, after adjusting for DQ, DPA1*02:01-DPB1*11:01 and DPA1*01:03-DPB1*03:01 were found to have opposite associations with progression (HR = 1.98 and 0.70, P = 0.021 and 6.16*10-3, respectively). Third, DRB1*03:01-DRB3*01:01 and DRB1*03:01-DRB3*02:02, sharing the DRB1*03:01, had opposite associations (HR = 0.73 and 1.44, P = 0.04 and 0.019, respectively), indicating a role of DRB3. Meanwhile, DRB1*12:01-DRB3*02:02 and DRB1*01:03 alone were found to associate with progression (HR = 2.6 and 2.32, P = 0.018 and 0.039, respectively). Fourth, through enumerating all heterodimers, it was found that both DQ and DP could exhibit associations with disease progression.RESULTSFirst, the current investigation updated the previously reported genetic associations of DQA1*03:01-DQB1*03:02 (hazard ratio [HR] = 1.25, P = 3.50*10-3) and DQA1*03:03-DQB1*03:01 (HR = 0.56, P = 1.16*10-3), and also uncovered a risk association with DQA1*05:01-DQB1*02:01 (HR = 1.19, P = 0.041). Second, after adjusting for DQ, DPA1*02:01-DPB1*11:01 and DPA1*01:03-DPB1*03:01 were found to have opposite associations with progression (HR = 1.98 and 0.70, P = 0.021 and 6.16*10-3, respectively). Third, DRB1*03:01-DRB3*01:01 and DRB1*03:01-DRB3*02:02, sharing the DRB1*03:01, had opposite associations (HR = 0.73 and 1.44, P = 0.04 and 0.019, respectively), indicating a role of DRB3. Meanwhile, DRB1*12:01-DRB3*02:02 and DRB1*01:03 alone were found to associate with progression (HR = 2.6 and 2.32, P = 0.018 and 0.039, respectively). Fourth, through enumerating all heterodimers, it was found that both DQ and DP could exhibit associations with disease progression.These results suggest that HLAII polymorphisms influence progression from islet autoimmunity to T1D among at-risk subjects with islet autoantibodies.CONCLUSIONSThese results suggest that HLAII polymorphisms influence progression from islet autoimmunity to T1D among at-risk subjects with islet autoantibodies.
OBJECTIVE To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Next-generation targeted sequencing was used to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants from the Diabetes Prevention Trial-1 and Randomized Diabetes Prevention Trial with Oral Insulin sponsored by TrialNet. By the linkage disequilibrium, DQA1 and DQB1 are haplotyped to form DQ haplotypes; DP and DR haplotypes are similarly constructed. Together with available clinical covariables, we applied the Cox regression model to assess HLAII immunogenic associations with the disease progression. RESULTS First, the current investigation updated the previously reported genetic associations of DQA1*03:01-DQB1*03:02 (hazard ratio [HR] = 1.25, P = 3.50*10−3) and DQA1*03:03-DQB1*03:01 (HR = 0.56, P = 1.16*10−3), and also uncovered a risk association with DQA1*05:01-DQB1*02:01 (HR = 1.19, P = 0.041). Second, after adjusting for DQ, DPA1*02:01-DPB1*11:01 and DPA1*01:03-DPB1*03:01 were found to have opposite associations with progression (HR = 1.98 and 0.70, P = 0.021 and 6.16*10−3, respectively). Third, DRB1*03:01-DRB3*01:01 and DRB1*03:01-DRB3*02:02, sharing the DRB1*03:01, had opposite associations (HR = 0.73 and 1.44, P = 0.04 and 0.019, respectively), indicating a role of DRB3. Meanwhile, DRB1*12:01-DRB3*02:02 and DRB1*01:03 alone were found to associate with progression (HR = 2.6 and 2.32, P = 0.018 and 0.039, respectively). Fourth, through enumerating all heterodimers, it was found that both DQ and DP could exhibit associations with disease progression. CONCLUSIONS These results suggest that HLAII polymorphisms influence progression from islet autoimmunity to T1D among at-risk subjects with islet autoantibodies.
To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D). Next-generation targeted sequencing was used to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants from the Diabetes Prevention Trial-1 and Randomized Diabetes Prevention Trial with Oral Insulin sponsored by TrialNet. By the linkage disequilibrium, DQA1 and DQB1 are haplotyped to form DQ haplotypes; DP and DR haplotypes are similarly constructed. Together with available clinical covariables, we applied the Cox regression model to assess HLAII immunogenic associations with the disease progression. First, the current investigation updated the previously reported genetic associations of DQA1*03:01-DQB1*03:02 (hazard ratio [HR] = 1.25, P = 3.50*10-3) and DQA1*03:03-DQB1*03:01 (HR = 0.56, P = 1.16*10-3), and also uncovered a risk association with DQA1*05:01-DQB1*02:01 (HR = 1.19, P = 0.041). Second, after adjusting for DQ, DPA1*02:01-DPB1*11:01 and DPA1*01:03-DPB1*03:01 were found to have opposite associations with progression (HR = 1.98 and 0.70, P = 0.021 and 6.16*10-3, respectively). Third, DRB1*03:01-DRB3*01:01 and DRB1*03:01-DRB3*02:02, sharing the DRB1*03:01, had opposite associations (HR = 0.73 and 1.44, P = 0.04 and 0.019, respectively), indicating a role of DRB3. Meanwhile, DRB1*12:01-DRB3*02:02 and DRB1*01:03 alone were found to associate with progression (HR = 2.6 and 2.32, P = 0.018 and 0.039, respectively). Fourth, through enumerating all heterodimers, it was found that both DQ and DP could exhibit associations with disease progression. These results suggest that HLAII polymorphisms influence progression from islet autoimmunity to T1D among at-risk subjects with islet autoantibodies.
Author Nelson, Wyatt C.
Skyler, Jay S.
Pyo, Chul-Woo
Zhao, Lue Ping
Papadopoulos, George K.
Geraghty, Daniel E.
Parikh, Hemang M.
Wang, Ruihan
Moustakas, Antonis K.
Pugliese, Alberto
Kwok, William W.
Bondinas, George P.
Lybrand, Terry P.
Lernmark, Åke
AuthorAffiliation 11 Department of Clinical Sciences, Lund University CRC, Skåne University Hospital, Malmö, Sweden
5 Department of Diabetes Immunology, City of Hope, South Pasadena, CA
7 Benaroya Research Institute, Seattle, WA
1 Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
6 Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL
10 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
8 Department of Chemistry, Vanderbilt University, Nashville, TN
2 School of Public Health, University of Washington, Seattle, WA
4 Diabetes Research Institute and Division of Endocrinology, Diabetes & Metabolism, University of Miami Miler School of Medicine, Miami, FL
9 Department of Food Science and Technology, Faculty of Environmental Sciences, Ionian University, Argostoli, Cephalonia, Greece
3 Laboratory of Biophysics, Biochemistry, Biomaterials and Bioprocessing, Faculty of Agricultural Technology, Technological Educati
AuthorAffiliation_xml – name: 1 Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
– name: 10 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
– name: 7 Benaroya Research Institute, Seattle, WA
– name: 4 Diabetes Research Institute and Division of Endocrinology, Diabetes & Metabolism, University of Miami Miler School of Medicine, Miami, FL
– name: 11 Department of Clinical Sciences, Lund University CRC, Skåne University Hospital, Malmö, Sweden
– name: 3 Laboratory of Biophysics, Biochemistry, Biomaterials and Bioprocessing, Faculty of Agricultural Technology, Technological Educational Institute of Epirus, Arta, Greece
– name: 5 Department of Diabetes Immunology, City of Hope, South Pasadena, CA
– name: 9 Department of Food Science and Technology, Faculty of Environmental Sciences, Ionian University, Argostoli, Cephalonia, Greece
– name: 2 School of Public Health, University of Washington, Seattle, WA
– name: 6 Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL
– name: 8 Department of Chemistry, Vanderbilt University, Nashville, TN
Author_xml – sequence: 1
  givenname: Lue Ping
  orcidid: 0000-0002-1387-7165
  surname: Zhao
  fullname: Zhao, Lue Ping
– sequence: 2
  givenname: George K.
  orcidid: 0000-0002-6944-6591
  surname: Papadopoulos
  fullname: Papadopoulos, George K.
– sequence: 3
  givenname: Jay S.
  orcidid: 0000-0003-1136-8110
  surname: Skyler
  fullname: Skyler, Jay S.
– sequence: 4
  givenname: Alberto
  surname: Pugliese
  fullname: Pugliese, Alberto
– sequence: 5
  givenname: Hemang M.
  surname: Parikh
  fullname: Parikh, Hemang M.
– sequence: 6
  givenname: William W.
  surname: Kwok
  fullname: Kwok, William W.
– sequence: 7
  givenname: Terry P.
  surname: Lybrand
  fullname: Lybrand, Terry P.
– sequence: 8
  givenname: George P.
  surname: Bondinas
  fullname: Bondinas, George P.
– sequence: 9
  givenname: Antonis K.
  surname: Moustakas
  fullname: Moustakas, Antonis K.
– sequence: 10
  givenname: Ruihan
  surname: Wang
  fullname: Wang, Ruihan
– sequence: 11
  givenname: Chul-Woo
  surname: Pyo
  fullname: Pyo, Chul-Woo
– sequence: 12
  givenname: Wyatt C.
  surname: Nelson
  fullname: Nelson, Wyatt C.
– sequence: 13
  givenname: Daniel E.
  surname: Geraghty
  fullname: Geraghty, Daniel E.
– sequence: 14
  givenname: Åke
  orcidid: 0000-0003-1735-0499
  surname: Lernmark
  fullname: Lernmark, Åke
BackLink https://www.ncbi.nlm.nih.gov/pubmed/38498185$$D View this record in MEDLINE/PubMed
https://lup.lub.lu.se/record/db7beeb0-f3a9-45ef-a6a3-1bda9a1ff373$$DView record from Swedish Publication Index
oai:portal.research.lu.se:publications/db7beeb0-f3a9-45ef-a6a3-1bda9a1ff373$$DView record from Swedish Publication Index
BookMark eNqNkttuEzEQhleoiB7gghdAlrhpJZb6mF1foaihbaSIBgjqpeX1zjauNvZib1r1DXksvE0KtAiJi5Gt8e9vfo9nP9tx3kGWvSb4PWWsOK4NZTmRvHiW7RHJRC4EL3eyPUy4zIWUdDfbj_EaY8x5Wb7IdlnJZUlKsZf9OJ-N0UmrY0TTKTpEky_oHZp8TjFHR-gMHER0CQHQV-h00D20d2gcozc27Wt0afsl6peA5sFfBYjReodOg18lffDGuxsI97neowsXoUe-QYu7DhBBE6sr6BN_vPLuCs116K2xnXZ9RNahxa3_LZkHuAHXD6RFsLqN6HAyX-QEaVejxSdcHL3MnjcpD6-260H27fTj4uQ8n12cTU_Gs9xwyfqciYZxyoQhIzzCvClBGkJZXRRcUmYo5pJQQjQuJeYVJlo0EohoOEigKc0OMr3hxlvo1pXqgl3pcKe8tqrzodetSn0AHcxStWsVQSVVa40ezEdVV0UFUGHVMC0VF9AoPdJMkarWUpOmYQVLNWb_rNGuuxTVlv2fuA8bXGKtoDapkSHZfOT80YmzS3XlbxQhmDNKy0Q43BKC_76G2KuVjQbaVjvw66ioHJWSUo6HYm-fSK_9Orj0JYphQUTJRmJQvfnT0i8vD4OZBMcbgQk-xpDeZWx_38Pk0LaKYDWMvhpGXw2jn24cPbnxAP1b-xN3rAPG
CitedBy_id crossref_primary_10_1007_s00125_024_06274_6
crossref_primary_10_2337_dc24_0573
crossref_primary_10_3390_jcm14020383
Cites_doi 10.2337/db09-0680
10.1056/NEJMoa012350
10.1007/s00125-008-1047-3
10.1111/tan.12258
10.1001/jama.2017.17070
10.2337/db07-1331
10.2337/db12-1387
10.1034/j.1399-0039.2000.560303.x
10.4049/jimmunol.176.3.1988
10.1111/j.1399-5448.2011.00774.x
10.1007/s11892-018-1113-2
10.2337/dc19-2547
10.2337/db18-0882
10.2337/diabetes.49.1.121
10.2337/dc21-1628
10.1038/nrdp.2017.16
10.1016/0198-8859(93)90526-7
10.1210/jc.2005-1166
10.2337/db19-0273
10.2337/dbi19-0022
10.1016/j.cct.2004.08.002
10.2337/dc21-1251
10.1111/joim.13648
10.1016/j.humimm.2015.05.001
10.2337/diab.44.6.608
10.1038/ajg.2015.150
10.1111/j.1744-313X.2008.00749.x
10.1073/pnas.2214331119
10.1111/j.1469-1809.1989.tb01802.x
10.2337/diacare.28.5.1068
10.1007/s00592-013-0526-2
10.2337/db07-1736
10.2337/dc18-2282
10.4049/jimmunol.1800723
ContentType Journal Article
Copyright 2024 by the American Diabetes Association.
Copyright American Diabetes Association May 2024
2024 by the American Diabetes Association 2024
Copyright_xml – notice: 2024 by the American Diabetes Association.
– notice: Copyright American Diabetes Association May 2024
– notice: 2024 by the American Diabetes Association 2024
CorporateAuthor Lunds universitet
Profile areas and other strong research environments
Department of Clinical Sciences, Malmö
Lund University
Celiac Disease and Diabetes Unit
Strategiska forskningsområden (SFO)
EXODIAB: Excellence of Diabetes Research in Sweden
Faculty of Medicine
Celiaki och diabetes
Strategic research areas (SRA)
Medicinska fakulteten
Profilområden och andra starka forskningsmiljöer
Institutionen för kliniska vetenskaper, Malmö
CorporateAuthor_xml – name: Faculty of Medicine
– name: Medicinska fakulteten
– name: Strategiska forskningsområden (SFO)
– name: Celiaki och diabetes
– name: Celiac Disease and Diabetes Unit
– name: Institutionen för kliniska vetenskaper, Malmö
– name: Strategic research areas (SRA)
– name: Lunds universitet
– name: Profilområden och andra starka forskningsmiljöer
– name: Lund University
– name: EXODIAB: Excellence of Diabetes Research in Sweden
– name: Profile areas and other strong research environments
– name: Department of Clinical Sciences, Malmö
DBID AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
K9.
NAPCQ
7X8
5PM
ADTPV
AOWAS
D95
DOI 10.2337/dc23-1947
DatabaseName CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
ProQuest Health & Medical Complete (Alumni)
Nursing & Allied Health Premium
MEDLINE - Academic
PubMed Central (Full Participant titles)
SwePub
SwePub Articles
SWEPUB Lunds universitet
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
ProQuest Health & Medical Complete (Alumni)
Nursing & Allied Health Premium
MEDLINE - Academic
DatabaseTitleList
MEDLINE - Academic
ProQuest Health & Medical Complete (Alumni)
MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
EISSN 1935-5548
EndPage 834
ExternalDocumentID oai_portal_research_lu_se_publications_db7beeb0_f3a9_45ef_a6a3_1bda9a1ff373
oai_lup_lub_lu_se_db7beeb0_f3a9_45ef_a6a3_1bda9a1ff373
PMC11043228
38498185
10_2337_dc23_1947
Genre Journal Article
GrantInformation_xml – fundername: NIDDK NIH HHS
  grantid: R01 DK132406
– fundername: ;
  grantid: R01 DK132406
GroupedDBID ---
-ET
..I
.XZ
08P
0R~
18M
29F
2WC
4.4
53G
5GY
5RE
5RS
5VS
6PF
8R4
8R5
AAFWJ
AAIKC
AAMNW
AAWTL
AAYEP
AAYXX
ABOCM
ABPPZ
ACGFO
ACGOD
ADBBV
AEGXH
AENEX
AERZD
AFOSN
AFRAH
AHMBA
AIAGR
ALIPV
ALMA_UNASSIGNED_HOLDINGS
BAWUL
BENPR
BTFSW
CITATION
CS3
DIK
DU5
E3Z
EBS
EDB
EMOBN
EX3
F5P
GX1
H13
HZ~
IAO
IEA
IHR
INH
INR
IOF
IPO
KQ8
L7B
M0K
M5~
O5R
O5S
O9-
OK1
OVD
P2P
PCD
Q2X
RHI
SV3
TDI
TEORI
TR2
TWZ
VVN
W8F
WH7
WOQ
WOW
YHG
YOC
ZCG
~KM
CGR
CUY
CVF
ECM
EIF
NPM
K9.
NAPCQ
7X8
5PM
ADTPV
AOWAS
D95
.55
.GJ
3O-
41~
7RV
7X2
7X7
88E
88I
8AF
8AO
8C1
8F7
8FE
8FH
8FI
8FJ
8G5
AAKAS
AAQOH
AAQQT
AAYJJ
ABUWG
ADZCM
AFFNX
AFKRA
AI.
AN0
AQUVI
ATCPS
AZQEC
BCR
BCU
BEC
BHPHI
BKEYQ
BKNYI
BLC
BNQBC
BPHCQ
BVXVI
C1A
CCPQU
DWQXO
EJD
FYUFA
GNUQQ
GUQSH
HCIFZ
HMCUK
IAG
ITC
J5H
K9-
M0R
M0T
M1P
M2O
M2P
M2Q
N4W
PEA
PHGZM
PHGZT
PJZUB
PPXIY
PQQKQ
PROAC
PSQYO
PUEGO
S0X
SJFOW
UKHRP
VH1
WHG
X7M
ZGI
ZXP
ID FETCH-LOGICAL-c493t-35f34235c160604f8e9c123d774923c20491211a08904b01a5f9e15f4e9e21a03
ISSN 0149-5992
1935-5548
IngestDate Thu Aug 28 04:26:26 EDT 2025
Thu Jul 03 05:08:07 EDT 2025
Thu Aug 21 18:26:14 EDT 2025
Fri Jul 11 13:43:31 EDT 2025
Mon Jun 30 07:25:22 EDT 2025
Mon Jul 21 05:57:13 EDT 2025
Thu Apr 24 23:05:27 EDT 2025
Tue Jul 01 04:29:30 EDT 2025
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 5
Language English
License 2024 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/journals/pages/license.
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c493t-35f34235c160604f8e9c123d774923c20491211a08904b01a5f9e15f4e9e21a03
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ORCID 0000-0002-1387-7165
0000-0003-1136-8110
0000-0002-6944-6591
0000-0003-1735-0499
OpenAccessLink https://www.ncbi.nlm.nih.gov/pmc/articles/11043228
PMID 38498185
PQID 3051583653
PQPubID 47715
PageCount 9
ParticipantIDs swepub_primary_oai_portal_research_lu_se_publications_db7beeb0_f3a9_45ef_a6a3_1bda9a1ff373
swepub_primary_oai_lup_lub_lu_se_db7beeb0_f3a9_45ef_a6a3_1bda9a1ff373
pubmedcentral_primary_oai_pubmedcentral_nih_gov_11043228
proquest_miscellaneous_2968922403
proquest_journals_3051583653
pubmed_primary_38498185
crossref_citationtrail_10_2337_dc23_1947
crossref_primary_10_2337_dc23_1947
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2024-05-01
PublicationDateYYYYMMDD 2024-05-01
PublicationDate_xml – month: 05
  year: 2024
  text: 2024-05-01
  day: 01
PublicationDecade 2020
PublicationPlace United States
PublicationPlace_xml – name: United States
– name: Alexandria
PublicationTitle Diabetes care
PublicationTitleAlternate Diabetes Care
PublicationYear 2024
Publisher American Diabetes Association
Publisher_xml – name: American Diabetes Association
References Hagopian (2024041918520745000_B18) 2011; 12
Hadley (2024041918520745000_B15) 2015; 110
SEARCH Study Group (2024041918520745000_B1) 2004; 25
Parviainen (2024041918520745000_B35) 2022; 45
Bonifacio (2024041918520745000_B4) 2014; 51
Rewers (2024041918520745000_B16) 2018; 18
(2024041918520745000_B24) 2002; 346
Krischer (2024041918520745000_B26) 2017; 318
Katsarou (2024041918520745000_B2) 2017; 3
Krischer (2024041918520745000_B23) 2017; 318
Marquis (2024041918520745000_B6) 2000; 56
Al-Jenaidi (2024041918520745000_B7) 2005; 90
James (2024041918520745000_B30) 2018; 201
Williams (2024041918520745000_B10) 2008; 51
Klobuch (2024041918520745000_B33) 2022; 119
Vehik (2024041918520745000_B34) 2020; 43
Zhao (2024041918520745000_B21) 2022; 45
Hippich (2024041918520745000_B19) 2019; 68
Varney (2024041918520745000_B14) 2010; 59
Erlich (2024041918520745000_B29) 2013; 62
Gogolin (2024041918520745000_B9) 1989; 53
James (2024041918520745000_B32) 2020; 69
Hu (2024041918520745000_B5) 1993; 38
Erlich (2024041918520745000_B8) 2008; 57
Lernmark (2024041918520745000_B17) 2023; 294
Pugliese (2024041918520745000_B22) 1995; 44
Zhao (2024041918520745000_B12) 2019; 68
Skyler (2024041918520745000_B25) 2005; 28
Krischer (2024041918520745000_B3) 2019; 42
Noble (2024041918520745000_B13) 2000; 49
Cejkova (2024041918520745000_B11) 2008; 35
Ozaki (2024041918520745000_B28) 2014; 83
Ettinger (2024041918520745000_B31) 2006; 176
Butty (2024041918520745000_B20) 2008; 57
Nelson (2024041918520745000_B27) 2015; 76
References_xml – volume: 59
  start-page: 2055
  year: 2010
  ident: 2024041918520745000_B14
  article-title: HLA DPA1, DPB1 alleles and haplotypes contribute to the risk associated with type 1 diabetes: analysis of the type 1 diabetes genetics consortium families
  publication-title: Diabetes
  doi: 10.2337/db09-0680
– volume: 346
  start-page: 1685
  year: 2002
  ident: 2024041918520745000_B24
  article-title: Effects of insulin in relatives of patients with type 1 diabetes mellitus
  publication-title: N EnglJ Med
  doi: 10.1056/NEJMoa012350
– volume: 51
  start-page: 1444
  year: 2008
  ident: 2024041918520745000_B10
  article-title: Autoantibodies to islet antigen-2 are associated with HLA-DRB1*07 and DRB1*09 haplotypes as well as DRB1*04 at onset of type 1 diabetes: the possible role of HLA-DQA in autoimmunity to IA-2
  publication-title: Diabetologia
  doi: 10.1007/s00125-008-1047-3
– volume: 83
  start-page: 10
  year: 2014
  ident: 2024041918520745000_B28
  article-title: HLA-DRB1, -DRB3, -DRB4 and -DRB5 genotyping at a super-high resolution level by long range PCR and high-throughput sequencing
  publication-title: Tissue Antigens
  doi: 10.1111/tan.12258
– volume: 318
  start-page: 1891
  year: 2017
  ident: 2024041918520745000_B26
  article-title: Effect of oral insulin on prevention of diabetes in relatives of patients with type 1 diabetes: a randomized clinical trial
  publication-title: JAMA
  doi: 10.1001/jama.2017.17070
– volume: 57
  start-page: 1084
  year: 2008
  ident: 2024041918520745000_B8
  article-title: HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families
  publication-title: Diabetes
  doi: 10.2337/db07-1331
– volume: 62
  start-page: 2618
  year: 2013
  ident: 2024041918520745000_B29
  article-title: Next generation sequencing reveals the association of DRB3*02:02 with type 1 diabetes
  publication-title: Diabetes
  doi: 10.2337/db12-1387
– volume: 318
  start-page: 1891
  year: 2017
  ident: 2024041918520745000_B23
  article-title: Effect of oral insulin on prevention of diabetes in relatives of patients with type 1 diabetes: a randomized clinical trial
  publication-title: JAMA
  doi: 10.1001/jama.2017.17070
– volume: 56
  start-page: 217
  year: 2000
  ident: 2024041918520745000_B6
  article-title: HLA-DRB1 and DQB1 genotypes in patients with insulin-dependent neonatal diabetes mellitus. A study of 13 cases
  publication-title: Tissue Antigens
  doi: 10.1034/j.1399-0039.2000.560303.x
– volume: 176
  start-page: 1988
  year: 2006
  ident: 2024041918520745000_B31
  article-title: Allelic variation in key peptide-binding pockets discriminates between closely related diabetes-protective and diabetes-susceptible HLA-DQB1*06 alleles
  publication-title: J Immunol
  doi: 10.4049/jimmunol.176.3.1988
– volume: 12
  start-page: 733
  year: 2011
  ident: 2024041918520745000_B18
  article-title: The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants
  publication-title: Pediatr Diabetes
  doi: 10.1111/j.1399-5448.2011.00774.x
– volume: 18
  start-page: 136
  year: 2018
  ident: 2024041918520745000_B16
  article-title: The Environmental Determinants of Diabetes in the Young (TEDDY) study: 2018 update
  publication-title: Curr Diab Rep
  doi: 10.1007/s11892-018-1113-2
– volume: 43
  start-page: 2066
  year: 2020
  ident: 2024041918520745000_B34
  article-title: Hierarchical order of distinct autoantibody spreading and progression to type 1 diabetes in the TEDDY study
  publication-title: Diabetes Care
  doi: 10.2337/dc19-2547
– volume: 68
  start-page: 847
  year: 2019
  ident: 2024041918520745000_B19
  article-title: Genetic contribution to the divergence in type 1 diabetes risk between children from the general population and children from affected families
  publication-title: Diabetes
  doi: 10.2337/db18-0882
– volume: 49
  start-page: 121
  year: 2000
  ident: 2024041918520745000_B13
  article-title: The HLA class II locus DPB1 can influence susceptibility to type 1 diabetes
  publication-title: Diabetes
  doi: 10.2337/diabetes.49.1.121
– volume: 45
  start-page: 1610
  year: 2022
  ident: 2024041918520745000_B21
  article-title: Association of HLA-DQ heterodimer residues −18β and β57 with progression from islet autoimmunity to diabetes in the Diabetes Prevention Trial-Type 1
  publication-title: Diabetes Care
  doi: 10.2337/dc21-1628
– volume: 3
  start-page: 17016
  year: 2017
  ident: 2024041918520745000_B2
  article-title: Type 1 diabetes mellitus
  publication-title: Nat Rev Dis Primers
  doi: 10.1038/nrdp.2017.16
– volume: 38
  start-page: 105
  year: 1993
  ident: 2024041918520745000_B5
  article-title: Association of insulin-dependent diabetes mellitus in Taiwan with HLA class II DQB1 and DRB1 alleles
  publication-title: Hum Immunol
  doi: 10.1016/0198-8859(93)90526-7
– volume: 90
  start-page: 5104
  year: 2005
  ident: 2024041918520745000_B7
  article-title: Contribution of selective HLA-DRB1/DQB1 alleles and haplotypes to the genetic susceptibility of type 1 diabetes among Lebanese and Bahraini Arabs
  publication-title: J Clin Endocrinol Metab
  doi: 10.1210/jc.2005-1166
– volume: 68
  start-page: 1692
  year: 2019
  ident: 2024041918520745000_B12
  article-title: Eleven amino acids of HLA-DRB1 and fifteen amino acids of HLA-DRB3, 4, and 5 include potentially causal residues responsible for the risk of childhood type 1 diabetes
  publication-title: Diabetes
  doi: 10.2337/db19-0273
– volume: 69
  start-page: 1311
  year: 2020
  ident: 2024041918520745000_B32
  article-title: T-cell epitopes and neo-epitopes in type 1 diabetes: a comprehensive update and reappraisal
  publication-title: Diabetes
  doi: 10.2337/dbi19-0022
– volume: 25
  start-page: 458
  year: 2004
  ident: 2024041918520745000_B1
  article-title: SEARCH for Diabetes in Youth: a multicenter study of the prevalence, incidence and classification of diabetes mellitus in youth
  publication-title: Control Clin Trials
  doi: 10.1016/j.cct.2004.08.002
– volume: 45
  start-page: 871
  year: 2022
  ident: 2024041918520745000_B35
  article-title: Heterogeneity of type 1 diabetes at diagnosis supports existence of age-related endotypes
  publication-title: Diabetes Care
  doi: 10.2337/dc21-1251
– volume: 294
  start-page: 145
  year: 2023
  ident: 2024041918520745000_B17
  article-title: Possible heterogeneity of initial pancreatic islet beta-cell autoimmunity heralding type 1 diabetes
  publication-title: J Intern Med
  doi: 10.1111/joim.13648
– volume: 76
  start-page: 928
  year: 2015
  ident: 2024041918520745000_B27
  article-title: An integrated genotyping approach for HLA and other complex genetic systems
  publication-title: Hum Immunol
  doi: 10.1016/j.humimm.2015.05.001
– volume: 44
  start-page: 608
  year: 1995
  ident: 2024041918520745000_B22
  article-title: HLA-DQB1*0602 is associated with dominant protection from diabetes even among islet cell antibody-positive first-degree relatives of patients with IDDM
  publication-title: Diabetes
  doi: 10.2337/diab.44.6.608
– volume: 110
  start-page: 915
  year: 2015
  ident: 2024041918520745000_B15
  article-title: HLA-DPB1*04:01 protects genetically susceptible children from celiac disease autoimmunity in the TEDDY study
  publication-title: Am J Gastroenterol
  doi: 10.1038/ajg.2015.150
– volume: 35
  start-page: 133
  year: 2008
  ident: 2024041918520745000_B11
  article-title: HLA DRB1, DQB1 and insulin promoter VNTR polymorphisms: interactions and the association with adult-onset diabetes mellitus in Czech patients
  publication-title: Int J Immunogenet
  doi: 10.1111/j.1744-313X.2008.00749.x
– volume: 119
  start-page: e2214331119
  year: 2022
  ident: 2024041918520745000_B33
  article-title: Human T cells recognize HLA-DP-bound peptides in two orientations
  publication-title: Proc Natl Acad Sci USA
  doi: 10.1073/pnas.2214331119
– volume: 53
  start-page: 327
  year: 1989
  ident: 2024041918520745000_B9
  article-title: Subtypes of HLA-DQ and -DR defined by DQB1 and DRB1 RFLPs: allele frequencies in the general population and in insulin-dependent diabetes (IDDM) and multiple sclerosis patients
  publication-title: Ann Hum Genet
  doi: 10.1111/j.1469-1809.1989.tb01802.x
– volume: 28
  start-page: 1068
  year: 2005
  ident: 2024041918520745000_B25
  article-title: Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial–Type 1
  publication-title: Diabetes Care
  doi: 10.2337/diacare.28.5.1068
– volume: 51
  start-page: 403
  year: 2014
  ident: 2024041918520745000_B4
  article-title: A strategy to find gene combinations that identify children who progress rapidly to type 1 diabetes after islet autoantibody seroconversion
  publication-title: Acta Diabetol
  doi: 10.1007/s00592-013-0526-2
– volume: 57
  start-page: 2348
  year: 2008
  ident: 2024041918520745000_B20
  article-title: Impact of diabetes susceptibility loci on progression from pre-diabetes to diabetes in at-risk individuals of the diabetes prevention trial-type 1 (DPT-1)
  publication-title: Diabetes
  doi: 10.2337/db07-1736
– volume: 42
  start-page: 1051
  year: 2019
  ident: 2024041918520745000_B3
  article-title: Predicting islet cell autoimmunity and type 1 diabetes: an 8-year TEDDY study progress report
  publication-title: Diabetes Care
  doi: 10.2337/dc18-2282
– volume: 201
  start-page: 3524
  year: 2018
  ident: 2024041918520745000_B30
  article-title: DRB4*01:01 has a distinct motif and presents a proinsulin epitope that is recognized in subjects with type 1 diabetes
  publication-title: J Immunol
  doi: 10.4049/jimmunol.1800723
SSID ssj0004488
Score 2.4754968
Snippet To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D)....
OBJECTIVE To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes...
To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes...
OBJECTIVE: To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes...
SourceID swepub
pubmedcentral
proquest
pubmed
crossref
SourceType Open Access Repository
Aggregation Database
Index Database
Enrichment Source
StartPage 826
SubjectTerms Alleles
Autoantibodies
Autoimmunity
Clinical Medicine
Clinical trials
Diabetes
Diabetes mellitus (insulin dependent)
Diabetes Mellitus, Type 1 - genetics
Diabetes Mellitus, Type 1 - prevention & control
Disease prevention
Disease Progression
DQA1 protein
Drb1 protein
Endocrinology and Diabetes
Endokrinologi och diabetes
Gene Frequency
Genes
Genotype
Haplotypes
Histocompatibility antigen HLA
HLA-DQ beta-Chains - genetics
HLA-DRB1 Chains - genetics
Humans
Immunogenicity
Klinisk medicin
Linkage disequilibrium
Medical and Health Sciences
Medicin och hälsovetenskap
Original
Pathogenesis
Regression models
Research design
Seroconversion
Title HLA Class II ( DR , DQ, DP ) Genes Were Separately Associated With the Progression From Seroconversion to Onset of Type 1 Diabetes Among Participants in Two Diabetes Prevention Trials (DPT-1 and TN07)
URI https://www.ncbi.nlm.nih.gov/pubmed/38498185
https://www.proquest.com/docview/3051583653
https://www.proquest.com/docview/2968922403
https://pubmed.ncbi.nlm.nih.gov/PMC11043228
https://lup.lub.lu.se/record/db7beeb0-f3a9-45ef-a6a3-1bda9a1ff373
oai:portal.research.lu.se:publications/db7beeb0-f3a9-45ef-a6a3-1bda9a1ff373
Volume 47
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3dT9swELeASYiXad_rxqbbtAdQly6JkzR-RJSJ8rUwFYF4ifLhCLSSVLTVxP6__V-7s_NV4IHxkKhyXDvu_Xq-O59_ZuwLl37flllsJKZEByUTqRHbIjFMOxFxn_M00Vm-R97uibN35p4tLa-3spbms7iX_Ll3X8ljpIplKFfaJfsfkq0bxQL8jPLFO0oY7w-S8e7Blj7Vsjsckqk4UFkNg2N1D8jhJ1bpafdUXkvUCormW45vapmgsXmq4rCIlYAStTRJB1qzxRVpkULlpKuAGtmoP_KpVIkD5Lx2re6gittuqROLgqhM0abMmsu8O_pdNFUqqihsaaR-GfW-wciw1PLF6MisgxKlqVx_lZLTWvFtFds9mOMbV7OuWgGbRGkxKebjohXq7-736gjSr5tyz-NehOqyLg_QfyCiDL3Zh7LMi3YgxHaatMPW3gNUis3gbwG8iqAKwxX6AL6e1FpfcNdAu8pvTwuaCLSEv9vS8b7ttc0FHYu9PRPZXHEZpInNDUvotlqInFwpSHLfEWQxNZNxnSIZHG6jZeagvvWX2RMbnSAVMBjuN7t-HXWqaj0gzZtFHX-ru11jq1Ufi4bXHW_qblLwAnWuMrdGz9jT0k-CLQ3652xJ5i_Y6mGZCfKS_UXsg8I-DIewMfj5FQbHeAWboDAPhHloMA8N5oEwD4h5aGEeCPOwiHmYFaAwD0UGhHmwoBI7KMxDG_NwmQNivqnSYB405vE9CfGAiAdC_OYrdvJ9Z7S9a5RHkhiJI_jM4G5GlJluYnnEOpX5UiRo-6XoRKGnlNjobxNnYmT6wnRi04rcTEjLzRwppI3F_DVbyYtcvmVg85j3hZVyL7WcvmnHiU9cjxYarajdM9FhG5W8wqTk66djY8Yh-u0k5ZCkHJKUO-xzXXWiSWruq7ReCT0sddg05HTEk889l3fYp_oxzjC0bBjlsphPQ1t4viDLH-u80Ripe6nA1WH-AnrqCsRev_gkv7xQLPYVujtsRwNt4Tvj-QSvGK9wKsM07sdSxmaY8UiEjovjjLwIxxWnkYisLON9fLnze9rRQYywZE67KNubtJZEHtT4u8eP7z1ba7TVOluZXc_lB3RkZvFH9X_-Bz-pSx0
linkProvider Flying Publisher
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=HLA+Class+II+%28DR%2C+DQ%2C+DP%29+Genes+Were+Separately+Associated+With+the+Progression+From+Seroconversion+to+Onset+of+Type+1+Diabetes+Among+Participants+in+Two+Diabetes+Prevention+Trials+%28DPT-1+and+TN07%29&rft.jtitle=Diabetes+care&rft.au=Zhao%2C+Lue+Ping&rft.au=Papadopoulos%2C+George+K.&rft.au=Skyler%2C+Jay+S.&rft.au=Pugliese%2C+Alberto&rft.date=2024-05-01&rft.pub=American+Diabetes+Association&rft.issn=0149-5992&rft.eissn=1935-5548&rft.volume=47&rft.issue=5&rft.spage=826&rft.epage=834&rft_id=info:doi/10.2337%2Fdc23-1947&rft_id=info%3Apmid%2F38498185&rft.externalDocID=PMC11043228
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0149-5992&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0149-5992&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0149-5992&client=summon