Jacobi, Thomas and Massier, Lucas and Kloeting, Nora and Horn, Katrin and Schuch, Alexander and Ahnert, Peter and Engel, Christoph and Loeffler, Markus and Burkhardt, Ralph and Thiery, Joachim and Toenjes, Anke and Stumvoll, Michael and Blueher, Matthias and Doxiadis, Llias and Scholz, Markus and Kovacs, Peter (2020) HLA Class II Allele Analyses Implicate Common Genetic Components in Type 1 and Non-Insulin-Treated Type 2 Diabetes. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 105 (3). E245-E254. ISSN 0021-972X, 1945-7197
Full text not available from this repository. (Request a copy)Abstract
Context: Common genetic susceptibility may underlie the frequently observed co-occurrence of type 1 and type 2 diabetes in families. Given the role of HLA class II genes in the pathophysiology of type 1 diabetes, the aim of the present study was to test the association of high density imputed human leukocyte antigen (HLA) genotypes with type 2 diabetes. Objectives and Design: Three cohorts (N-total = 10 413) from Leipzig, Germany were included in this study: LIFE-Adult (N = 4649), LIFE-Heart (N = 4815) and the Sorbs (N = 949) cohort. Detailed metabolic phenotyping and genome-wide single nucleotide polymorphism (SNP) data were available for all subjects. Using 1000 Genome imputation data, HLA genotypes were imputed on 4-digit level and association tests for type 2 diabetes, and related metabolic traits were conducted. Results: In a meta-analysis including all 3 cohorts, the absence of HLA-DRB5 was associated with increased risk of type 2 diabetes (P = 0.001). In contrast, HLA-DQB*06:02 and HLA-DQA*01:02 had a protective effect on type 2 diabetes (P = 0.005 and 0.003, respectively). Both alleles are part of the well-established type 1 diabetes protective haplotype DRB1*15:01 similar to DQA1*01:02 similar to D QB1*06:02, which was also associated with reduced risk of type 2 diabetes (OR 0.84; P = 0.005). On the contrary, the DRB1*07:01 similar to DQA1*02:01 similar to DQB1*03:03 was identified as a risk haplotype in non-insulin-treated diabetes (OR 1.37; P = 0.002). Conclusions: Genetic variation in the HLA class II locus exerts risk and protective effects on non-insulin-treated type 2 diabetes. Our data suggest that the genetic architecture of type 1 diabetes and type 2 diabetes might share common components on the HLA class II locus.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SELF-CONTAINED POPULATION; GENOME-WIDE ASSOCIATION; MELLITUS; RISK; PEPTIDE; BINDING; SUSCEPTIBILITY; GLUCOSE; HETEROGENEITY; PROTECTION; HLA class II; single nucleotide polymorphism; genotype imputation; haplotype; type 1 diabetes; type 2 diabetes; association |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Mar 2021 10:35 |
| Last Modified: | 29 Mar 2021 10:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45003 |
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