HLA Class II Allele Analyses Implicate Common Genetic Components in Type 1 and Non-Insulin-Treated Type 2 Diabetes


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 (Ntotal = 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-DQB06:02 and HLA-DQA01:02 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 DRB115:01~DQA101:02DQB106:02, which was also associated with reduced risk of type 2 diabetes (OR 0.84; P = 0.005). On the contrary, the DRB107:01DQA102:01~DQB103:03 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.

DOI: 10.1210/clinem/dgaa027

Projects: Genetical Statistics and Systems Biology

Publication type: Journal article

Journal: The Journal of clinical endocrinology and metabolism

Human Diseases: No Human Disease specified

Citation: The Journal of Clinical Endocrinology & Metabolism 105(3):e245-e254

Date Published: 1st Mar 2020

Registered Mode: imported from a bibtex file

Authors: Thomas Jacobi, Lucas Massier, Nora Klöting, Katrin Horn, Alexander Schuch, Peter Ahnert, Christoph Engel, Markus Löffler, Ralph Burkhardt, Joachim Thiery, Anke Tönjes, Michael Stumvoll, Matthias Blüher, Ilias Doxiadis, Markus Scholz, Peter Kovacs

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Jacobi, T., Massier, L., Klöting, N., Horn, K., Schuch, A., Ahnert, P., Engel, C., Löffler, M., Burkhardt, R., Thiery, J., Tönjes, A., Stumvoll, M., Blüher, M., Doxiadis, I., Scholz, M., & Kovacs, P. (2020). HLA Class II Allele Analyses Implicate Common Genetic Components in Type 1 and Non–Insulin-Treated Type 2 Diabetes. In The Journal of Clinical Endocrinology & Metabolism (Vol. 105, Issue 3, pp. e245–e254). The Endocrine Society. https://doi.org/10.1210/clinem/dgaa027

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Created: 15th Sep 2020 at 08:49

Last updated: 7th Dec 2021 at 17:58

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