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Association of HLA Genotype and Fulminant Type 1 Diabetes in Koreans
곽수헌,김윤지,채제수,이현규,한범,김종일,정규성,조영민,박경수 한국유전체학회 2015 Genomics & informatics Vol.13 No.4
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 level 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 Korean Reference Panel. 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). 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 for fulminant T1DM in Koreans. Further large-scale research is required to confirm these findings.