Yamamoto Takuma, Tanaka Hidekazu, Emoto Yuko, Umehara Takahiro, Fukahori Yuki, Kuriu Yukiko, Matoba Ryoji, Ikematsu Kazuya
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.
Laboratory of Pharmacology, Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Japan.
Brain Dev. 2014 Jun;36(6):479-83. doi: 10.1016/j.braindev.2013.07.011. Epub 2013 Aug 19.
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.
Single nucleotide polymorphisms of the CPT2 gene were investigated among 54 SUDI cases and 200 healthy volunteers.
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).
The F352C CPT2 variant might be a genetic risk factor for SUDI.
肉碱棕榈酰转移酶（CPT）II是线粒体脂肪酸氧化过程中的关键酶之一，在同时节省葡萄糖以及满足长时间禁食或运动等主要能量供应需求时对能量产生至关重要。当婴儿所需能量超过糖酵解系统所能提供的能量时，他们依赖线粒体脂肪酸氧化途径。据报道，CPT2基因突变可导致婴儿猝死（SUDI）。最近有报道称，CPT2基因多态性（F352C）的不耐热表型会降低CPT II酶活性。F352C变异在高温下会导致能量危机，并被怀疑是急性脑病的危险因素。然而，尚未描述CPT2基因多态性与SUDI之间的关系。
在54例SUDI病例和200名健康志愿者中研究了CPT2基因的单核苷酸多态性。
SUDI组中C等位基因的频率显著高于对照组[25.0%对16.0%，优势比（OR）=1.75，95%置信区间（CI）=1.05 - 2.92，p = 0.030]。SUDI组中F352C纯合子的频率显著高于对照组（11.1%对3.5%，OR = 3.45，95% CI = 1.11 - 10.73，p = 0.036）。
F352C CPT2变异可能是SUDI的遗传危险因素。
