%0 Journal Article %1 Jacobi2020-xb %A Jacobi, Thomas %A Massier, Lucas %A Klöting, Nora %A Horn, Katrin %A Schuch, Alexander %A Ahnert, Peter %A Engel, Christoph %A Löffler, Markus %A Burkhardt, Ralph %A Thiery, Joachim %A Tönjes, Anke %A Stumvoll, Michael %A Blüher, Matthias %A Doxiadis, Ilias %A Scholz, Markus %A Kovacs, Peter %D 2020 %I The Endocrine Society %J J. Clin. Endocrinol. Metab. %K 1 2 HLA II; association; class diabetes diabetes; genotype haplotype; imputation; nucleotide polymorphism; single type %N 3 %P e245--e254 %T HLA class II allele analyses implicate common genetic components in type 1 and non-insulin-treated type 2 diabetes %V 105 %X 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-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~DQA1*01:02~DQB1*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~DQA1*02:01~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.

@article{Jacobi2020-xb, 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 (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-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~DQA1*01:02~DQB1*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~DQA1*02:01~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.}, added-at = {2024-09-10T11:54:51.000+0200}, author = {Jacobi, Thomas and Massier, Lucas and Kl{\"o}ting, Nora and Horn, Katrin and Schuch, Alexander and Ahnert, Peter and Engel, Christoph and L{\"o}ffler, Markus and Burkhardt, Ralph and Thiery, Joachim and T{\"o}njes, Anke and Stumvoll, Michael and Bl{\"u}her, Matthias and Doxiadis, Ilias and Scholz, Markus and Kovacs, Peter}, biburl = {https://puma.scadsai.uni-leipzig.de/bibtex/288cd61c80d6d33d2f9bb2e66394c69bf/scadsfct}, copyright = {https://academic.oup.com/journals/pages/open\_access/funder\_policies/chorus/standard\_publication\_model}, interhash = {0bbe6df4674216edbaaf1ef474896b4a}, intrahash = {88cd61c80d6d33d2f9bb2e66394c69bf}, journal = {J. Clin. Endocrinol. Metab.}, keywords = {1 2 HLA II; association; class diabetes diabetes; genotype haplotype; imputation; nucleotide polymorphism; single type}, language = {en}, month = mar, number = 3, pages = {e245--e254}, publisher = {The Endocrine Society}, timestamp = {2024-09-10T13:58:29.000+0200}, title = {{HLA} class {II} allele analyses implicate common genetic components in type 1 and non-insulin-treated type 2 diabetes}, volume = 105, year = 2020 }