Protective association of HLA-DPB104:01:01 with acute encephalopathy with biphasic seizures and late reduced diffusion identified by HLA imputation

• Published in: Genes and immunity 2022-06, Vol.23 (3-4), p.123-128
• Main Authors: Kasai, Mariko, Omae, Yosuke, Khor, Seik-Soon, Shibata, Akiko, Hoshino, Ai, Mizuguchi, Masashi, Tokunaga, Katsushi
• Format: Article
• Language: English
• Subjects: 45/43; 631/208/205/2138; 631/250/256/2516; Alleles; Antigens; Biomedical and Life Sciences; Biomedicine; Cancer Research; Coma; Confidence intervals; Convulsions & seizures; Encephalopathy; Fever; Gene Expression; Gene frequency; Gene mapping; Genes; Genome-wide association studies; Genomes; Genotyping; Haplotypes; Histocompatibility antigen HLA; Human Genetics; Immunology; Infections; Kinases; Pathogenesis; Pediatrics; Quality control; Seizures; Single-nucleotide polymorphism; Viral infections
• ISSN: 1476-5470; 1466-4879; 1476-5470
• DOI: 10.1038/s41435-022-00170-y

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a severe syndrome of acute encephalopathy that affects infants and young children. AESD is a polygenic disorder preceded by common viral infections with high fever. We conducted an association study of human leukocyte antigen ( HLA ) regions with AESD using HLA imputation. SNP genotyping was performed on 254 Japanese patients with AESD and 799 healthy controls. We conducted 3-field HLA imputation for 14 HLA genes based on Japanese-specific references using data from our previous genome-wide association study. After quality control, 208 patients and 737 controls were included in the analysis of HLA alleles. We then compared the carrier frequencies of HLA alleles and haplotypes between the patients and controls. HLA-DPB1*04:01:01 showed a significant association with AESD, exerting a protective effect against the disease ( p  = 0.0053, p corrected  = 0.042, odds ratio = 0.43, 95% confidence interval = 0.21–0.80). The allele frequency of HLA-DPB1*04:01:01 was lower in East Asians than in Caucasians, which may partially account for the higher incidence of AESD in the Japanese population. The present results demonstrate the importance of fine-mapping of the HLA region to investigate disease susceptibilities and elucidate the pathogenesis of AESD.