Cited by 68Diabetes and associated disordersGenetic Associations and EpidemiologyDiabetes Management and Research

HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 Haplotype Protects Autoantibody-Positive Relatives From Type 1 Diabetes Throughout the Stages of Disease Progression

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Pugliese, Alberto, Boulware, David, Yu, Liping, Babu, Sunanda, Steck, Andrea K., Becker, Dorothy, Rodriguez, Henry, DiMeglio, Linda +8 more·2016·Diabetes

Abstract

The HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is linked to protection from the development of type 1 diabetes (T1D). However, it is not known at which stages in the natural history of T1D development this haplotype affords protection. We examined a cohort of 3,358 autoantibody-positive relatives of T1D patients in the Pathway to Prevention (PTP) Study of the Type 1 Diabetes TrialNet. The PTP study examines risk factors for T1D and disease progression in relatives. HLA typing revealed that 155 relatives carried this protective haplotype. A comparison with 60 autoantibody-negative relatives suggested protection from autoantibody development. Moreover, the relatives with DRB1*15:01-DQA1*01:02-DQB1*06:02 less frequently expressed autoantibodies associated with higher T1D risk, were less likely to have multiple autoantibodies at baseline, and rarely converted from single to multiple autoantibody positivity on follow-up. These relatives also had lower frequencies of metabolic abnormalities at baseline and exhibited no overall metabolic worsening on follow-up. Ultimately, they had a very low 5-year cumulative incidence of T1D. In conclusion, the protective influence of DRB1*15:01-DQA1*01:02-DQB1*06:02 spans from autoantibody development through all stages of progression, and relatives with this allele only rarely develop T1D.

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Crossref · 10.2337/db15-1105

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Authors
Pugliese, A., Boulware, D., Yu, L., Babu, S., Steck, A. K., Becker, D., Rodriguez, H., DiMeglio, L., Evans-Molina, C., Harrison, L. C., Schatz, D., Palmer, J. P., Greenbaum, C., Eisenbarth, G. S., Sosenko, J. M., & the Type 1 Diabetes TrialNet Study Group
Affiliations
  • University of Miami (US)
  • University of South Florida (US)
  • University of Colorado Anschutz (US)
  • University of Pittsburgh (US)
  • Department of Pediatric Endocrinology, Riley Hospital for Children at Indiana University Health, Indianapolis, IN
  • Richard L. Roudebush VA Medical Center (US)
  • The University of Melbourne (AU)
  • University of Florida Health (US)
  • University of Washington (US)
Corresponding author
Pugliese, Alberto
Venue
Diabetes
Published
2016-01-28
Volume
65
Issue
4
Pages
1109-1119
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
OpenAlex
W2258562835
Cited by
68
References
52
Citations by year
2026: 5 · 2025: 6 · 2024: 8 · 2023: 3 · 2022: 8 · 2021: 4 · 2020: 7 · 2019: 9 · 2018: 11 · 2017: 4 · 2016: 3
FWCI
7.25
Type
journal article
Language
en
Open access
Locations
  • Diabetes (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
  • Purdue University Indianapolis (Indiana University) (submittedVersion)
  • PMC
Funders
  • National Institutes of Health (U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085465, U01 DK085453, U01 DK085461, U01 DK085463, U01 DK085466, U01 DK085499, U01 DK085504, U01 DK085505, U01 DK085509, U01 DK103180, U01 DK103153, U01 DK085476, U01 DK103266)
  • JDRF
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
type 1 diabetes, protective HLA alleles, autoantibody production, disease progression, metabolic abnormalities, type 1 diabetes prevention
MeSH terms
Adolescent, Adult, Autoantibodies, Child, Child, Preschool, Diabetes Mellitus, Type 1, Family, Female, Haplotypes, Humans, Male, Risk Factors, Disease Progression, Genetic Predisposition to Disease, Diabetes Complications, Young Adult, HLA-DRB1 Chains, HLA-DQ alpha-Chains, HLA-DQ beta-Chains

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