Takuma Yamamoto1, Hidekazu Tanaka2, Yuko Emoto3, Takahiro Umehara4, Yuki Fukahori5, Yukiko Kuriu3, Ryoji Matoba3, Kazuya Ikematsu4. 1. Division of Forensic Pathology and Science, Unit of Social Medicine, Course of Medical and Dental Sciences, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Japan; Department of Legal Medicine, Osaka University Graduate School of Medicine, Japan. Electronic address: t-yamamoto@nagasaki-u.ac.jp. 2. Laboratory of Pharmacology, Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Japan. 3. Department of Legal Medicine, Osaka University Graduate School of Medicine, Japan. 4. Division of Forensic Pathology and Science, Unit of Social Medicine, Course of Medical and Dental Sciences, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Japan. 5. Division of Forensic Pathology and Science, Unit of Social Medicine, Course of Medical and Dental Sciences, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Japan; Forensic Science Laboratory, Nagasaki Prefectural Police Headquarters, Japan.
Abstract
RATIONALE: Carnitine palmitoyltransferase (CPT) II is one of a pivotal enzyme in mitochondrial fatty acid oxidation, which is essential for energy production during simultaneous glucose sparing and a requirement for major energy supply, such as prolonged fasting or exercise. When infants require more energy than provided by the glycolytic system, they rely on the mitochondrial fatty acid oxidation pathway. Mutations of the CPT2 gene have been reported to cause sudden unexpected death in infancy (SUDI). A thermolabile phenotype of a CPT2 polymorphism (F352C) has been recently reported to reduce CPT II enzyme activity. The F352C variant results in energy crisis at high temperature and is suspected as a risk factor for acute encephalopathy. However, a relationship between CPT2 gene polymorphism and SUDI has not been described. METHODS: Single nucleotide polymorphisms of the CPT2 gene were investigated among 54 SUDI cases and 200 healthy volunteers. RESULTS: The frequency of the C allele was significantly higher in the SUDI group than in the control group [25.0% vs 16.0%, odds ratio (OR)=1.75, 95% confidence interval (CI)=1.05-2.92, p=0.030). The frequency of the F352C homozygote was significantly higher in the SUDI group than in control group (11.1% vs 3.5%, OR=3.45, 95% CI=1.11-10.73, p=0.036). CONCLUSION: The F352C CPT2 variant might be a genetic risk factor for SUDI.
RATIONALE: Carnitine palmitoyltransferase (CPT) II is one of a pivotal enzyme in mitochondrial fatty acid oxidation, which is essential for energy production during simultaneous glucose sparing and a requirement for major energy supply, such as prolonged fasting or exercise. When infants require more energy than provided by the glycolytic system, they rely on the mitochondrial fatty acid oxidation pathway. Mutations of the CPT2 gene have been reported to cause sudden unexpected death in infancy (SUDI). A thermolabile phenotype of a CPT2 polymorphism (F352C) has been recently reported to reduce CPT II enzyme activity. The F352C variant results in energy crisis at high temperature and is suspected as a risk factor for acute encephalopathy. However, a relationship between CPT2 gene polymorphism and SUDI has not been described. METHODS: Single nucleotide polymorphisms of the CPT2 gene were investigated among 54 SUDI cases and 200 healthy volunteers. RESULTS: The frequency of the C allele was significantly higher in the SUDI group than in the control group [25.0% vs 16.0%, odds ratio (OR)=1.75, 95% confidence interval (CI)=1.05-2.92, p=0.030). The frequency of the F352C homozygote was significantly higher in the SUDI group than in control group (11.1% vs 3.5%, OR=3.45, 95% CI=1.11-10.73, p=0.036). CONCLUSION: The F352CCPT2 variant might be a genetic risk factor for SUDI.