Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Association of HLA Genotype and Fulminant Type 1 Diabetes in Koreans

  • Kwak, Soo Heon (Department of Internal Medicine, Seoul National University Hospital) ;
  • Kim, Yoon Ji (Department of Internal Medicine, Seoul National University Hospital) ;
  • Chae, Jeesoo (Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Lee, Cue Hyunkyu (Asan Institute for Life Sciences, Asan Medical Center) ;
  • Han, Buhm (Asan Institute for Life Sciences, Asan Medical Center) ;
  • Kim, Jong-Il (Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Jung, Hye Seung (Department of Internal Medicine, Seoul National University Hospital) ;
  • Cho, Young Min (Department of Internal Medicine, Seoul National University Hospital) ;
  • Park, Kyong Soo (Department of Internal Medicine, Seoul National University Hospital)
  • Received : 2015.11.30
  • Accepted : 2015.12.17
  • Published : 2015.12.31
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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 $HLA-DR{\beta}1$ 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.

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References

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