[P1-1~141] Poster Presentation 1

[P1-31] Association of COX Gene Polymorphism with Acute Necrotizing Encephalopathy

^○Ai HOSHINO^{1, 2} (1.Department of Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, 2.Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan)

[Purpose] Acute necrotizing encephalopathy (ANE) is prevalent in young children in East Asia. The exact pathogenesis remains unclear, although the difference in incidence among ethnics suggests the involvement of host genetic factors in ANE. A familial and recurrent variant occurring in Caucasian ethnics, ANE1, is caused by missense mutations in RANBP2 gene, a gene encoding a nuclear pore protein. In this study, we focused on Cox11, which reportedly modulates hexokinase activity via binding to RANBP2 in CNS. We hypothesized that COX11 variants may be a genetic risk factor of ANE. We further examined COX10 gene and COX15 gene known as causative genes of Leigh syndrome.
[Methods] We recruited 31 Japanese ANE patients. We examined mutation and SNPs in whole exons of COX10, COX11 and COX15 genes by PCR amplification and direct sequencing. Genotype and allele frequencies were compared between ANE patients and controls.
[Results] No mutations of COX10, COX11 and COX15 genes were found in ANE patients. The allele frequency of T at the missense variant, rs2230351, in COX10 gene exon3 was significantly higher in ANE (29.0%) than in controls (13.4%) (p=0.01).
[Conclusions] Allele T at rs2230351 in COX10 gene was a predisposing factor in ANE. According to the database from Exome Aggregation Consortium, this allele frequency was higher in East Asian (11.5%) than in other ethnics. The difference among ethnics may account for the high prevalence of ANE in Asia.