ArticleDiabetes2009
Do non-HLA genes influence development of persistent islet autoimmunity and type 1 diabetes in children with high-risk HLA-DR,DQ genotypes?
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 51 citations in OpenAlex.
- Interaction BetweenNutrients · 2025Observational
- Primary hyperaldosteronism associated with type 3 autoimmune polyendocrine syndrome: A rare case report.Clinical case reports · 2024Article
- Next-generation sequencing reveals additional HLA class I and class II alleles associated with type 1 diabetes and age at onset.Frontiers in immunology · 2024Article
- Influence ofFrontiers in immunology · 2021Review
- DNA methylation near the INS gene is associated with INS genetic variation (rs689) and type 1 diabetes in the Diabetes Autoimmunity Study in the Young.Pediatric diabetes · 2020Article
- What Have Slow Progressors Taught Us About T1D-Mind the Gap!Current diabetes reports · 2019Review
- Loss of B-Cell Anergy in Type 1 Diabetes Is Associated With High-Risk HLA and Non-HLA Disease Susceptibility Alleles.Diabetes · 2018Article
- Genetic Risk Scores for Type 1 Diabetes Prediction and Diagnosis.Current diabetes reports · 2017Review
- Beta-cell Specific Autoantibodies: Are they Just an Indicator of Type 1 Diabetes?Current diabetes reviews · 2017Review
- Phenome-Wide Association Study to Explore Relationships between Immune System Related Genetic Loci and Complex Traits and Diseases.PloS one · 2016Article
- Non-HLA type 1 diabetes genes modulate disease risk together with HLA-DQ and islet autoantibodies.Genes and immunity · 2015Article
- Tyrosine phosphatase PTPN22: multifunctional regulator of immune signaling, development, and disease.Annual review of immunology · 2014Review
- The next big idea.Diabetes technology & therapeutics · 2013Article
- Pathogenesis of type 1 diabetes: lessons from natural history studies of high-risk individuals.Annals of the New York Academy of Sciences · 2013Review
- Evidence of stage- and age-related heterogeneity of non-HLA SNPs and risk of islet autoimmunity and type 1 diabetes: the diabetes autoimmunity study in the young.Clinical & developmental immunology · 2013Article
- rs11203203 is associated with type 1 diabetes risk in population pre-screened for high-risk HLA-DR,DQ genotypes.Pediatric diabetes · 2012Article
- Role of immune system modulation in prevention of type 1 diabetes mellitus.Indian journal of endocrinology and metabolism · 2012Article
- Influence of type 1 diabetes genes on disease progression: similarities and differences between countries.Current diabetes reports · 2012Review
- Effect of the PTPN22 and INS risk genotypes on the progression to clinical type 1 diabetes after the initiation of β-cell autoimmunity.Diabetes · 2012Article
- Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveSpecific alleles of non-HLA genes INS, CTLA-4, and PTPN22 have been associated with type 1 diabetes. We examined whether some of these alleles influence development of islet autoimmunity or progression from persistent islet autoimmunity to type 1 diabetes in children with high-risk HLA-DR,DQ genotypes. RESEARCH DESIGN AND
methodsSince 1993, the Diabetes Autoimmunity Study in the Young (DAISY) has followed 2,449 young children carrying HLA-DR,DQ genotypes associated with type 1 diabetes. Of those, 112 have developed islet autoimmunity (persistent autoantibodies to insulin, GAD65, and/or IA-2), and 47 of these have progressed to type 1 diabetes. The influence of polymorphisms of INS(-23Hph1), CTLA-4(T17A), and PTPN22(R620W) on development of persistent islet autoimmunity and progression to type 1 diabetes was evaluated by parametric models and by survival analyses.
resultsPTPN22(R620W) allele T was associated with development of persistent islet autoimmunity (hazard ratio 1.83 [95% CI 1.27-2.63]) controlling for ethnicity, presence of HLA-DR3/4,DQB1*0302, and having a first-degree relative with type 1 diabetes. Survival analyses showed a significantly (P = 0.002) higher risk of persistent islet autoimmunity by age 10 years for the TT genotype (27.3%) than for the CT or CC genotype (7.9 and 5.3%, respectively). Cumulative risk of persistent islet autoimmunity was slightly higher (P = 0.02) for the INS(-23Hph1) AA genotype (7.8%) than for the AT or TT genotype (4.2 and 6.4% risk by age 10 years, respectively).
conclusionsWhereas the HLA-DR3/4,DQB1*0302 genotype had a dramatic influence on both development of islet autoimmunity and progression to type 1 diabetes, the PTPN22(R620W) T allele significantly influences progression to persistent islet autoimmunity in the DAISY cohort.
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