title: Apolipoprotein E-ε4 deficiency and cognitive function in hepatitis C virus-infected patients.
abstract: Hepatitis C virus (HCV) causes not only liver damage in certain patients but can also lead to neuropsychiatric symptoms. Previous studies have shown that the type 4 allele of the gene for apolipoprotein E (APOE) is strongly protective against HCV-induced damage in liver. In this study, we have investigated the possibility that APOE genotype is involved in the action of HCV in brain. One hundred HCV-infected patients with mild liver disease underwent a neurological examination and a comprehensive psychometric testing of attention and memory function. In addition, patients completed questionnaires for the assessment of fatigue, health-related quality of life and mood disturbances. Apolipoprotein E gene genotyping was carried out on saliva using buccal swabs. The APOE-ε4 allele frequency was significantly lower in patients with an impairment of working memory, compared to those with a normal working memory test result (P = 0.003). A lower APOE-ε4 allele frequency was also observed in patients with definitely altered attention ability (P = 0.008), but here, the P-value missed the level of significance after application of the Bonferroni correction. Our data suggest that the APOE-ε4 allele is protective against attention deficit and especially against poor working memory in HCV-infected subjects with mild liver disease. Considering the role of apolipoprotein E in the life cycle of the virus, the findings shed interesting new light upon possible pathomechanisms behind the development of neuropsychiatric symptoms in hepatitis C infection.
authors: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors: M A
authors: MA
authors: Wozniak
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: L M
authors: LM
authors: Lugo Iparraguirre
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: M
authors: M
authors: Dirks
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: Milani
authors: M
authors: Deb-Chatterji
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: H
authors: H
authors: Pflugrad
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: A
authors: A
authors: Goldbecker
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: A B
authors: AB
authors: Tryc
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: H
authors: H
authors: Worthmann
authors: Department of Gastroenterology and Hepatology, St George's Hospital and Medical School, London, UK.
authors: M
authors: M
authors: Gess
authors: Department of Medicine, St Mary's Hospital Campus, Imperial College London, London, UK.
authors: M M E
authors: MM
authors: Crossey
authors: Department of Gastroenterology and Hepatology, St George's Hospital and Medical School, London, UK.
authors: D M
authors: DM
authors: Forton
authors: Department of Medicine, St Mary's Hospital Campus, Imperial College London, London, UK.
authors: S D
authors: SD
authors: Taylor-Robinson
authors: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors: R F
authors: RF
authors: Itzhaki
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: K
authors: K
authors: Weissenborn
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4 / Q000172:deficiency* / Q000235:genetics; D003071:Cognition; D060825:Cognitive Dysfunction / Q000523:psychology* / Q000821:virology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics; D006501:Hepatic Encephalopathy / Q000523:psychology* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000473:pathology* / Q000821:virology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D019964:Mood Disorders / Q000523:psychology* / Q000821:virology; D019636:Neurodegenerative Diseases / Q000523:psychology* / Q000821:virology; D009483:Neuropsychological Tests; D011788:Quality of Life / Q000523:psychology; D011795:Surveys and Questionnaires
chemical_list: D053327:Apolipoprotein E4
keywords: attention; cerebral lipoprotein metabolism; hepatitis C virus encephalopathy; neurodegeneration; virus replication