title: Association of HLA Genotype and Fulminant Type 1 Diabetes in Koreans.
abstract: Fulminant type 1 diabetes (T1DM) is a distinct subtype of T1DM that is characterized by rapid onset hyperglycemia, ketoacidosis, absolute insulin deficiency, and near normal levels of glycated hemoglobin at initial presentation. Although it has been reported that class II human leukocyte antigen (HLA) genotype is associated with fulminant T1DM, the genetic predisposition is not fully understood. In this study we investigated the HLA genotype and haplotype in 11 Korean cases of fulminant T1DM using imputation of whole exome sequencing data and compared its frequencies with 413 participants of the Korean Reference Panel. The HLA-DRB1*04:05-HLA-DQB1*04:01 haplotype was significantly associated with increased risk of fulminant T1DM in Fisher's exact test (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.56 to 10.86; p = 0.009). A histidine residue at HLA-DRβ1 position 13 was marginally associated with increased risk of fulminant T1DM (OR, 2.45; 95% CI ,1.01 to 5.94; p = 0.054). Although we had limited statistical power, we provide evidence that HLA haplotype and amino acid change can be a genetic risk factor of fulminant T1DM in Koreans. Further large-scale research is required to confirm these findings.
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.
authors: Soo Heon
authors: SH
authors: Kwak
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.
authors: Yoon Ji
authors: YJ
authors: Kim
authors: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
authors: Jeesoo
authors: J
authors: Chae
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Korea.
authors: Cue Hyunkyu
authors: CH
authors: Lee
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Korea.; Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul 05505, Korea.
authors: Buhm
authors: B
authors: Han
authors: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
authors: Jong-Il
authors: JI
authors: Kim
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.
authors: Hye Seung
authors: HS
authors: Jung
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.; Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.
authors: Young Min
authors: YM
authors: Cho
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.; Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Korea.
authors: Kyong Soo
authors: KS
authors: Park
keywords: HLA antigens; autoimmunity; fulminant type 1 diabetes; haplotypes; imputation; whole exome sequencing