Functional rs6265 polymorphism in the brain-derived neurotrophic factor gene confers protection against neurocognitive dysfunction in posttraumatic stress disorder among Chinese patients with hepatocellular carcinoma

J Cell Biochem. 2019 Jun;120(6):10434-10443. doi: 10.1002/jcb.28328. Epub 2019 Jan 18.

Abstract

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that plagues trauma survivors. Evidence shows that brain-derived neurotrophic factor (BDNF) may be involved in the occurrence and development of PTSD. Here we tried to demonstrate whether BDNF gene polymorphisms are correlated with neurocognitive function following PTSD in patients with hepatocellular carcinoma (HCC). This study included 102 patients with HCC complicated with PTSD, 146 HCC patients, and 152 healthy volunteers. Initially, we evaluated the neurocognitive function of the study subjects. Next, we measured BDNF G11757C and rs6265 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. The correlation of BDNF polymorphisms and BDNF level with HCC complicated with PTSD was evaluated. The results revealed that HCC complicated with PTSD showed decreased serum BDNF level and Mini-mental state examination (MMSE) score. Serum BDNF level of HCC and HCC complicated with PTSD was positively correlated with MMSE score. GA + AA allele and A allele of rs6265 increased the risk of PTSD among patients with HCC. GA and AA genotypes of rs6265 were correlated with the decreased MMSE score of HCC complicated with PTSD. Haplotype GA of rs6265 and G11757C increased the risk of PTSD for HCC, while haplotype CG decreased this risk. Lastly, the logistic regression analysis suggested that low BDNF level was a contributor to HCC complicated with PTSD, while GG genotype of rs6265 served as a protective factor. Collectively, this study defines the GG genotype of BDNF rs6265 polymorphism as a protector to HCC complicated with PTSD. In addition, these results provided a promising target for PTSD prevention in patients with HCC.

Keywords: brain-derived neurotrophic factor (BDNF); gene polymorphism; hepatocellular carcinoma (HCC); neurocognitive function; posttraumatic stress disorder (PTSD).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People / genetics*
  • Brain-Derived Neurotrophic Factor / blood
  • Brain-Derived Neurotrophic Factor / genetics*
  • Carcinoma, Hepatocellular / physiopathology*
  • Carcinoma, Hepatocellular / psychology
  • Case-Control Studies
  • China / epidemiology
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / prevention & control*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Incidence
  • Liver Neoplasms / physiopathology
  • Liver Neoplasms / psychology
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Polymorphism, Single Nucleotide*
  • Stress Disorders, Post-Traumatic / complications*
  • Stress Disorders, Post-Traumatic / epidemiology

Substances

  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human