ArticleDiabetes, obesity & metabolism2009
The frequent and conserved DR3-B8-A1 extended haplotype confers less diabetes risk than other DR3 haplotypes.
Article in Diabetes, obesity & metabolism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Fifty years of HLA-associated type 1 diabetes risk: history, current knowledge, and future directions.Frontiers in immunology · 2024Review
- Article
- The next big idea.Diabetes technology & therapeutics · 2013Article
- Congruence as a measurement of extended haplotype structure across the genome.Journal of translational medicine · 2012Article
- The past, present, and future of genetic associations in type 1 diabetes.Current diabetes reports · 2011Review
- Replication and further characterization of a Type 1 diabetes-associated locus at the telomeric end of the major histocompatibility complex.Journal of diabetes · 2011Article
- The HLA-B 3906 allele imparts a high risk of diabetes only on specific HLA-DR/DQ haplotypes.Diabetologia · 2011Article
- Haplotype analysis discriminates genetic risk for DR3-associated endocrine autoimmunity and helps define extreme risk for Addison's disease.The Journal of clinical endocrinology and metabolism · 2010Article
- Banting Lecture 2009: An unfinished journey: molecular pathogenesis to prevention of type 1A diabetes.Diabetes · 2010Article
- Diubiquitin (Ubd) is a susceptibility gene for virus-triggered autoimmune diabetes in rats.Genes and immunityArticle
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
aimThe goal of this study was to develop and implement methodology that would aid in the analysis of extended high-density single nucleotide polymorphism (SNP) major histocompatibility complex (MHC) haplotypes combined with human leucocyte antigen (HLA) alleles in relation to type 1 diabetes risk.
methodsHigh-density SNP genotype data (2918 SNPs) across the MHC from the Type 1 Diabetes Genetics Consortium (1240 families), in addition to HLA data, were processed into haplotypes using PedCheck and Merlin, and extended DR3 haplotypes were analysed.
resultsWith this large dense set of SNPs, the conservation of DR3-B8-A1 (8.1) haplotypes spanned the MHC (>/=99% SNP identity). Forty-seven individuals homozygous for the 8.1 haplotype also shared the same homozygous genotype at four 'sentinel' SNPs (rs2157678 'T', rs3130380 'A', rs3094628 'C' and rs3130352 'T'). Conservation extended from HLA-DQB1 to the telomeric end of the SNP panels (3.4 Mb total). In addition, we found that the 8.1 haplotype is associated with lower risk than other DR3 haplotypes by both haplotypic and genotypic analyses [haplotype: p = 0.009, odds ratio (OR) = 0.65; genotype: p = 6.3 x 10(-5), OR = 0.27]. The 8.1 haplotype (from genotypic analyses) is associated with lower risk than the high-risk DR3-B18-A30 haplotype (p = 0.01, OR = 0.23), but the DR3-B18-A30 haplotype did not differ from other non-8.1 DR3 haplotypes relative to diabetes association.
conclusionThe 8.1 haplotype demonstrates extreme conservation (>3.4 Mb) and is associated with significantly lower risk for type 1 diabetes than other DR3 haplotypes.
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