Thermolabile polymorphism of carnitine palmitoyltransferase 2: A genetic risk factor of overall acute encephalopathy

• Published in: Brain & development (Tokyo. 1979) Vol. 41; no. 10; pp. 862 - 869
• Main Authors: Shibata, Akiko, Kasai, Mariko, Hoshino, Ai, Miyagawa, Taku, Matsumoto, Hiroshi, Yamanaka, Gaku, Kikuchi, Kenjiro, Kuki, Ichiro, Kumakura, Akira, Hara, Shinya, Shiihara, Takashi, Yamazaki, Sawako, Ohta, Masayasu, Yamagata, Takanori, Takanashi, Jun-ichi, Kubota, Masaya, Oka, Akira, Mizuguchi, Masashi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2019
• Subjects: Acute encephalitis with refractory; Acute encephalopathy; Acute encephalopathy with biphasic seizures and late reduced diffusion; Acute necrotizing encephalopathy; Alleles; Brain Diseases - genetics; Carnitine O-Palmitoyltransferase - deficiency; Carnitine O-Palmitoyltransferase - genetics; Carnitine palmitoyltransferase 2; Case-Control Studies; Child, Preschool; Clinically mild encephalitis/encephalopathy with reversible splenial lesion; Encephalitis; Energy failure; Female; Gene Frequency - genetics; Genetic risk factor; Genome-Wide Association Study - methods; Genotype; Humans; Infant; Japan; Male; Polymorphism, Genetic - genetics; Predisposing factor; Repetitive partial seizures/febrile infection-related epileptic syndrome; Risk Factors; Seizures; Susceptibility gene; Thermolability; Japan; Predisposing factor; Thermolability; Genetic risk factor; Acute encephalitis with refractory; Acute necrotizing encephalopathy; Repetitive partial seizures/febrile infection-related epileptic syndrome; Acute encephalopathy; Susceptibility gene; Acute encephalopathy with biphasic seizures and late reduced diffusion; Energy failure; Clinically mild encephalitis/encephalopathy with reversible splenial lesion; Carnitine palmitoyltransferase 2
• ISSN: 0387-7604; 1872-7131; 1872-7131
• DOI: 10.1016/j.braindev.2019.07.008

Acute encephalopathy is an acute brain dysfunction after preceding infection, consisting of multiple syndromes. Some syndromes, such as acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), are severe with poor outcome, whereas others, such as clinically mild encephalitis/encephalopathy with reversible splenial lesion (MERS), are mild with favorable outcome. Previous study reported the association of the thermolabile polymorphism in Carnitine Palmitoyltransferase 2 (CPT2) gene and severe syndromes of acute encephalopathy. To further explore the pathogenetic role of CPT2 in acute encephalopathy, we conducted a case-control association study of a typical thermolabile CPT2 polymorphism, rs2229291, in 416 patients of acute encephalopathy, including both severe and mild syndromes. The case cohort consisted of 416 patients, including AESD, MERS, and other syndromes. The control subjects were 100 healthy Japanese. rs2229291 was genotyped by Sanger sequencing. Genetic distribution was compared between the patients and controls using Cochran-Armitage trend test. Minor allele frequency of rs2229291 was significantly higher in AESD (p = 0.044), MERS (p = 0.015) and entire acute encephalopathy (p = 0.044) compared to the controls. The polymorphism showed no significant association with influenza virus, or with outcome. This study provided evidence that CPT2 is a susceptibility gene for overall acute encephalopathy, including both severe and mild syndromes, and suggested that impairment of mitochondrial metabolism is common to various syndromes of acute encephalopathy.