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HLA Class I and Genetic Susceptibility to Type 1 Diabetes
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OBJECTIVE: We report here genotyping data and type 1 diabetes association analyses for HLA class I loci (A, B, and C) on 1,753 multiplex pedigrees from the Type 1 Diabetes Genetics Consortium (T1DGC), a large international collaborative study. RESEARCH DESIGN AND METHODS: Complete eight-locus HLA genotyping data were generated. Expected patient class I (HLA-A, -B, and -C) allele frequencies were calculated, based on linkage disequilibrium (LD) patterns with observed HLA class II DRB1-DQA1-DQB1 haplotype frequencies. Expected frequencies were compared to observed allele frequencies in patients. RESULTS: Significant type 1 diabetes associations were observed at all class I HLA loci. After accounting for LD with HLA class II, the most significantly type 1 diabetes–associated alleles were B*5701 (odds ratio 0.19; P = 4 × 10−11) and B*3906 (10.31; P = 4 × 10−10). Other significantly type 1 diabetes–associated alleles included A*2402, A*0201, B*1801, and C*0501 (predisposing) and A*1101, A*3201, A*6601, B*0702, B*4403, B*3502, C*1601, and C*0401 (protective). Some alleles, notably B*3906, appear to modulate the risk of all DRB1-DQA1-DQB1 haplotypes on which they reside, suggesting a class I effect that is independent of class II. Other class I type 1 diabetes associations appear to be specific to individual class II haplotypes. Some apparent associations (e.g., C*1601) could be attributed to strong LD to another class I susceptibility locus (B*4403). CONCLUSIONS: These data indicate that HLA class I alleles, in addition to and independently from HLA class II alleles, are associated with type 1 diabetes.
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“The HLA region on chromosome 6 (ie, the IDDM1 locus) provides perhaps one-half of the genetic susceptibility that leads to risk of type 1 diabetes.73”
From Type 1 diabetes (2014) · cites this paper as [73]
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“Class I MHCs also seem to influence risk for type 1 diabetes, independent of class II molecules.73”
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Metadata
- Authors
- Noble, J. A., Valdes, A. M., Varney, M. D., Carlson, J. A., Moonsamy, P., Fear, A. L., Lane, J. A., Lavant, E., Rappner, R., Louey, A., Concannon, P., Mychaleckyj, J. C., Erlich, H. A., & for the Type 1 Diabetes Genetics Consortium
- Affiliations
- Children's Hospital Oakland Research Institute, Oakland, California;
- King's College London (GB)
- Australian Red Cross Lifeblood (AU)
- Skåne University Hospital (SE)
- Roche Molecular Systems, Pleasanton, California;
- University of Virginia (US)
- Corresponding author
- Noble, Janelle A.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2010-08-26
- Volume
- 59
- Issue
- 11
- Pages
- 2972-2979
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2963558
- OpenAlex
- W2110458118
- Cited by
- 254
- References
- 21
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 31 · 2023: 12 · 2022: 9 · 2021: 30 · 2020: 22 · 2019: 17 · 2018: 25 · 2017: 11 · 2016: 14 · 2015: 17 · 2014: 8 · 2013: 20 · 2012: 14
- FWCI
- 8.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Juvenile Diabetes Research Foundation International (U01 DK062418)
- National Human Genome Research Institute
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061722, R01 DK-61722, DK062418, U01DK062418)
- National Institute of Child Health and Human Development
- 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 › Clinical Neurology › Multiple Sclerosis Research Studies
- Keywords
- type 1 diabetes, HLA class I, HLA-A, HLA-B, HLA-C, genetic susceptibility, HLA class II, linkage disequilibrium, HLA-B*57:01, multiplex pedigrees, allele frequency
- MeSH terms
- Diabetes Mellitus, Type 1, Exons, Female, Gene Frequency, Humans, Male, Polymorphism, Genetic, T-Lymphocytes, HLA-A Antigens, HLA-B Antigens, HLA-C Antigens, Histocompatibility Antigens Class I, Linkage Disequilibrium, Genetic Predisposition to Disease, Insulin-Secreting Cells
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