HLA Class I and Genetic Susceptibility to Type 1 Diabetes

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.

• Publication year

  2010

• Venue

  Diabetes

• Publication date

  2010-08-26

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.2337/db10-0699PMID 20798335PMCID 2963558
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Genetic variation within the HLA class III influences T1D susceptibility conferred by high risk HLA haplotypes

  2009cited by this paper
• The HLA-B/-C haplotype block contains major determinants for host control of HIV

  2009cited by this paper
• Confirmation of HLA class II independent type 1 diabetes associations in the major histocompatibility complex including HLA‐B and HLA‐A

  2009cited by this paper
• HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk

  2008influential reference
• Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

  2007cited by this paper
• Multi-SNP Analysis of MHC Region Remarkable Conservation of HLA-A1-B8-DR3 Haplotype

  2006influential reference
• Multi-SNP Analysis of MHC Region

  2006cited by this paper
• Association of HLA-DPB1 alleles with type I diabetes mellitus in Slovak population.

  2006cited by this paper
• Human leukocyte antigen class I B and C loci contribute to Type 1 Diabetes (T1D) susceptibility and age at T1D onset.

  2005influential reference
• DPB1 alleles are associated with type 1 diabetes susceptibility in multiple ethnic groups.

  2004cited by this paper
• A Naturally Selected Dimorphism within the HLA-B44 Supertype Alters Class I Structure, Peptide Repertoire, and T Cell Recognition

  2003cited by this paper
• HLA genes associated with autoimmunity and progression to disease in type 1 diabetes.

  2003cited by this paper
• The association of specific HLA class I and II alleles with type 1 diabetes among Filipinos.

  2002cited by this paper
• The HLA class I A locus affects susceptibility to type 1 diabetes.

  2002influential reference
• Modeling of HLA class II susceptibility to Type I diabetes reveals an effect associated with DPB1

  2001cited by this paper
• The HLA-DPB1--associated component of the IDDM1 and its relationship to the major loci HLA-DQB1, -DQA1, and -DRB1.

  2001cited by this paper
• The HLA class II locus DPB1 can influence susceptibility to type 1 diabetes.

  2000cited by this paper
• HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors.

  2000cited by this paper
• Virtual DNA analysis--a new tool for combination and standardised evaluation of SSO, SSP and sequencing-based typing results.

  1998cited by this paper
• The Effect of HLA-B Allele on the IDDM Risk Defined by DRB1*04 Subtypes and DQB1*0302

  1997cited by this paper
• Mapping disease genes: family-based association studies.

  1995cited by this paper
• HLA DR antigens and susceptibility to insulin-dependent diabetes mellitus.

  1984influential reference

• Islet-derived T cells from both mice and humans recognize conserved insulin A-chain peptides presented by HLA-C*03:04.

  2026cites this paper
• Shed light on molecular immunogenetic pathophysiology of type 1 diabetes to improve advanced treatment strategies.

  2025cites this paper
• Long non-coding RNAs as a novel source of beta cell autoantigens in type 1 diabetes

  2025cites this paper
• HLA-C⁣∗0304 Associates With Beneficial Gut Microbiota and Later Onset of Type 1 Diabetes in Pediatric Cohorts

  2025cites this paper
• HLA Class I and II genes: A key factor for type one diabetes susceptibility

  2025cites this paper
• Humanized Mouse Models for Type 1 Diabetes

  2025cites this paper
• Bcl-2 and Bcl-xL in Diabetes: Contributions to Endocrine Pancreas Viability and Function

  2025cites this paper
• Linking epigenetic mechanisms of T cell dysfunction with pathophysiology of type 1 diabetes mellitus

  2025cites this paper
• Inhibition of cell-mediated immunity in type 1 diabetes by beta cell-targeted PD-1 agonists in pancreas tissue slices

  2025cites this paper
• Human insulin as both antigen and protector in type 1 diabetes

  2024cites this paper
• Immune checkpoint modulators in early clinical development for the treatment of type 1 diabetes

  2024cites this paper
• Next-generation sequencing reveals additional HLA class I and class II alleles associated with type 1 diabetes and age at onset

  2024cites this paper
• Deficiency of Trex1 leads to spontaneous development of type 1 diabetes

  2024cites this paper
• Advancing Animal Models of Human Type 1 Diabetes.

  2024cites this paper
• Immunopeptidome mining reveals a novel ERS-induced target in T1D

  2024cites this paper
• Autoimmune CD8+ T cells in type 1 diabetes: from single-cell RNA sequencing to T-cell receptor redirection

  2024cites this paper
• Status of islet transplantation and innovations to sustainable outcomes: novel sites, cell sources, and drug delivery strategies

  2024cites this paper
• Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes

  2024cites this paper
• Incidence of Helicobacter pylori in Type l Diabetes Mellitus Patients and Association with Certain HLA Alleles

  2024cites this paper
• What Not to Overlook in the Management of Patients with Type 2 Diabetes Mellitus: The Nephrological and Hepatological Perspectives

  2024cites this paper
• Gene-environment interaction in the pathophysiology of type 1 diabetes

  2024cites this paper
• Immune checkpoint inhibitors and endocrinopathies in pediatric brain tumor patients

  2024cites this paper
• Impact of hyperglycemia on immune cell function: a comprehensive review

  2024cites this paper
• Fifty years of HLA-associated type 1 diabetes risk: history, current knowledge, and future directions

  2024cites this paper
• Allelic variants of genes of the main histocompatibility complex in children with type 1 diabetes mellitus who became ill at preschool age

  2024cites this paper
• Structural and biochemical analysis of highly similar HLA-B allotypes differentially associated with type 1 diabetes

  2024cites this paper
• Enhancing HLA‐B27 antigen detection: Leveraging machine learning algorithms for flow cytometric analysis

  2024cites this paper
• Genetic association and machine learning improves discovery and prediction of type 1 diabetes

  2024cites this paper
• Differences in F pocket impact on HLA I genetic associations with autoimmune diabetes

  2024cites this paper
• Investigating the Association Between Family Socioeconomic Profile and Diabetes Control in Children: A Cross‐Sectional Study From Sudan

  2024cites this paper
• Clinical Features and HLA Genetics Differ in Children at Type 1 Diabetes Onset by Hispanic Ethnicity

  2024cites this paper
• Virus-induced diabetes mellitus, revisiting infection etiology in light of SARS-CoV-2.

  2024cites this paper
• Cracking the type 1 diabetes code: Genes, microbes, immunity, and the early life environment

  2024cites this paper
• Partitioning genetic effects on birthweight at classical human leukocyte antigen loci into maternal and fetal components, using structural equation modelling

  2023cites this paper
• The role of endoplasmic reticulum aminopeptidases in type 1 diabetes mellitus.

  2023cites this paper
• A genomic data archive from the Network for Pancreatic Organ donors with Diabetes

  2023cites this paper
• HLA Class I association with autoimmune diabetes in Chinese: Distinct implications in classic type 1 diabetes and LADA.

  2023cites this paper
• Polymorphisms in intron 1 of HLA-DRA differentially associate with type 1 diabetes and celiac disease and implicate involvement of complement system genes C4A and C4B

  2023cites this paper
• Complete HLA genotyping of type 1 diabetes patients and controls from Mali reveals both expected and novel disease associations

  2023cites this paper
• Type 1 diabetes mellitus in pediatric age group: A rising endemic

  2022cites this paper
• Genome-wide discovery for diabetes-dependent triglycerides-associated loci

  2022cites this paper
• Immunogenetic surveillance to histocompatibility

  2022cites this paper
• HLA-G-mediated immunological tolerance and autoimmunity

  2022cites this paper
• The longitudinal loss of islet autoantibody responses from diagnosis of type 1 diabetes occurs progressively over follow-up and is determined by low autoantibody titres, early-onset, and genetic variants

  2022cites this paper
• The complement system and human autoimmune diseases.

  2022cites this paper
• Dupilumab-related type 1 diabetes in a patient with atopic dermatitis: a case report

  2021cites this paper
• Differential HLA Association of GAD65 and IA2 Autoantibodies in North Indian Type 1 Diabetes Patients

  2021cites this paper
• The Role of β Cell Stress and Neo-Epitopes in the Immunopathology of Type 1 Diabetes

  2021cites this paper
• Development of type 2 diabetes and insulin resistance in people with HIV infection: Prevalence, incidence and associated factors

  2021cites this paper
• High‐fat diet prevents the development of autoimmune diabetes in NOD mice

  2021cites this paper
• SARS-CoV-2 Proteome Harbors Peptides Which Are Able to Trigger Autoimmunity Responses: Implications for Infection, Vaccination, and Population Coverage

  2021cites this paper
• The Multifactorial Progression from the Islet Autoimmunity to Type 1 Diabetes in Children

  2021cites this paper
• Using the T Cell Receptor as a Biomarker in Type 1 Diabetes

  2021cites this paper
• Index60 Identifies Individuals at Appreciable Risk for Stage 3 Among an Autoantibody-Positive Population With Normal 2-Hour Glucose Levels: Implications for Current Staging Criteria of Type 1 Diabetes.

  2021cites this paper
• Heterogeneity in the presentation of clinical type 1 diabetes defined by the level of risk conferred by human leukocyte antigen class II genotypes

  2021cites this paper
• Index60 as an additional diagnostic criterion for type 1 diabetes

  2021cites this paper
• Molecular mechanisms underlying hepatitis C virus infection-related diabetes.

  2021cites this paper
• Metabolic Diseases and Down Syndrome: How Are They Linked Together?

  2021cites this paper
• Insulin’s other life: an autoantigen in type 1 diabetes

  2021cites this paper
• Pathophysiology and Risk Factors of Diabetes

  2021cites this paper
• High‐resolution genotyping of HLA class I loci in children with type 1 diabetes and celiac disease

  2021cites this paper
• Human islet T cells are highly reactive to preproinsulin in type 1 diabetes

  2021cites this paper
• Immunogenetic Epidemiology of Type 1 Diabetes in 14 Continental Western European Countries

  2021cites this paper
• Marine Algae-Derived Bioactive Compounds: A New Wave of Nanodrugs?

  2021cites this paper
• HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes

  2021cites this paper
• A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes

  2021cites this paper
• The Positivity Rate of IA-2A and ZnT8A in the Chinese Han Population With Type 1 Diabetes Mellitus: Association With rs1143627 and rs1143643 Polymorphisms in the IL1B Gene

  2021cites this paper
• Polyvaccine: joining the links in the cascade of type 1 diabetes

  2021cites this paper
• Multifactorial Basis and Therapeutic Strategies in Metabolism-Related Diseases

  2021cites this paper
• Autoimmune alleles at the major histocompatibility locus modify melanoma susceptibility

  2021cites this paper
• Crosstalk Between Immunity System Cells and Pancreas. Transformation of Stem Cells Used in the 3D Bioprinting Process as a Personalized Treatment Method for Type 1 Diabetes

  2020cites this paper
• Diabetes and Genetics: A Relationship Between Genetic Risk Alleles, Clinical Phenotypes and Therapeutic Approaches.

  2020cites this paper
• The association of HLA-DP loci with autoimmune diabetes in Chinese.

  2020cites this paper
• Combined use of different antibody clones improves the efficiency of human leukocyte antigen B27 detection by flow cytometry

  2020cites this paper
• Genome-wide analyses disclose the distinctive HLA architecture and the pharmacogenetic landscape of the Somali population

  2020cites this paper
• Critical Review of Existing MHC I Immunopeptidome Isolation Methods

  2020cites this paper
• Significance of KIR like natural killer cell receptors in autoimmune disorders.

  2020cites this paper
• Can cinnamon spice down autoimmune diseases?

  2020cites this paper
• Upregulation of HLA Class I and Antiviral Tissue Responses in Hashimoto's Thyroiditis

  2020cites this paper
• Flavonoids and type 2 diabetes: Evidence of efficacy in clinical and animal studies and delivery strategies to enhance their therapeutic efficacy.

  2020cites this paper
• Sintilimab-Induced Autoimmune Diabetes in a Patient With the Anti-tumor Effect of Partial Regression

  2020cites this paper
• The Immunoproteasome: An Emerging Target in Cancer, Autoimmune and Neurological Disorders.

  2020cites this paper
• Targeting Glycoproteins as a therapeutic strategy for diabetes mellitus and its complications

  2020cites this paper
• Presumption of guilt for T cells in type 1 diabetes: lead culprits or partners in crime depending on age of onset?

  2020cites this paper
• T-Cell Epitopes and Neo-epitopes in Type 1 Diabetes: A Comprehensive Update and Reappraisal

  2020cites this paper
• HLA and sleep parameter associations in post-H1N1 narcolepsy type 1 patients and first-degree relatives.

  2020cites this paper
• Adverse events associated with immune checkpoint inhibitors: a new era in autoimmune diabetes.

  2020cites this paper
• Genetic profile considerations for induction of allogeneic chimerism as a therapeutic approach for type 1 diabetes mellitus.

  2020cites this paper
• Systematic Review of Polygenic Risk Scores for Type 1 and Type 2 Diabetes

  2020cites this paper
• Failed Genetic Protection: Type 1 Diabetes in the Presence of HLA-DQB1*06:02

  2020cites this paper
• Relevance of Essential Trace Elements in Nutrition and Drinking Water for Human Health and Autoimmune Disease Risk

  2020cites this paper
• Microbiome and Cellular Players in Type 1 Diabetes: From Pathogenesis to Protection

  2020cites this paper
• Identification of Immunodominant HIV-1 Epitopes Presented by HLA-C*12:02, a Protective Allele, Using an Immunopeptidomics Approach

  2019cites this paper
• Human Leukocyte Antigens (HLA) Genes Association in Type 1 Diabetic Nephropathy.

  2019cites this paper
• A New Pedigree-Based SNP Haplotype Method for Genomic Polymorphism and Genetic Studies

  2019cites this paper
• Type 1 Diabetes Risk in African-Ancestry Participants and Utility of an Ancestry-Specific Genetic Risk Score

  2019cites this paper
• Genetics Coming of Age in Type 1 Diabetes

  2019cites this paper
• Stem-cell based organ-on-a-chip models for diabetes research.

  2019cites this paper
• Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC

  2019cites this paper
• Diabetes Mellitus

  2019cites this paper