title: Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism affects sympathetic tone in a gender-specific way.
abstract: The Val/Val genotype of the brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) has been reported to affect human anxiety-related phenotypes. Substantial research has demonstrated that anxiety is associated with sympathetic activation, while sex steroid hormones have been shown to exert differential actions in regulating BDNF expression. Thus, we examined whether the BDNF variant modulates autonomic function in a gender-dependent manner. From 708 adults initially screened for medical and psychiatric illnesses, a final cohort of 583 drug-free healthy Han Chinese (355 males, 228 females; age 34.43±8.42 years) was recruited for BDNF genotyping (Val/Val: 136, 23.3%, Val/Met: 294, 50.4%, and Met/Met: 153, 26.2%). Time- and frequency-domain analyses of heart rate variability (HRV) were used to assess autonomic outflow to the heart. Significant genotype-by-gender interaction effects were found on HRV indices. Even after adjusting for possible confounders, male participants bearing the Val/Val genotype had significant increases in low frequency (LF), LF% and LF/high frequency (HF) ratio, indicating altered sympathovagal balance with increased sympathetic modulation, compared to male Met/Met homozygotes. Females, however, showed an opposite but non-significant pattern. These results suggest that the studied BDNF polymorphism is associated with sympathetic control in a gender-specific way. The findings here support the view that male subjects with the Val/Val genotype have increased risk of anxiety by association with sympathetic activation.
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chuan-Chia
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Chang
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Tien-Yu
authors.initials: TY
authors.lastname: Chen
authors.affiliation: Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Fang
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. Electronic address: hsy@ndmctsgh.edu.tw.
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Huang
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001007:Anxiety / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006339:Heart Rate / Q000235:genetics*; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013564:Sympathetic Nervous System / Q000502:physiology*; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human; D008715:Methionine; D014633:Valine
keywords: Autonomic nervous system (ANS); Brain-derived neurotrophic factor (BDNF); Heart rate variability (HRV); Polymorphism; Sympathetic control