Functional Ser205Leu polymorphism of the nerve growth factor receptor (NGFR) gene is associated with vagal autonomic dysregulation in humans.
Evidence indicates that reduced cardiac vagal (parasympathetic) tone, a robust cardiovascular risk factor, is a trait vulnerability marker of major depressive disorder (MDD). The Ser205/Ser205 genotype of the functional polymorphism (Ser205Leu) of the nerve growth factor receptor (NGFR), also called p75 neurotrophin receptor (p75(NTR)), gene is reported to increase the risk of MDD. Here, we hypothesized that the NGFR Ser205Leu polymorphism may have an effect on vagal control. A sample of 810 healthy, drug-free, unrelated Han Chinese (413 males, 397 females; mean age 35.17 ± 8.53 years) was included in the NGFR genotyping. Short-term heart rate variability (HRV) was used to assess vagus-mediated autonomic function. Potential HRV covariates, such as mood/anxiety status and serum metabolic parameters, were assessed. Homozygotes of the Ser205 allele had significantly lower high frequency power and root mean square of successive heartbeat interval differences, both HRV indices of vagal modulation, compared to Leu205 allele carriers. Even after adjusting for relevant confounders, these associations remained significant. Further stratification by sex revealed that the associations were observed only in males. Our results implicate that decreased parasympathetic activity is associated with the NGFR Ser205/Ser205 genotype in a gender-specific manner, suggesting a potential role of NGFR polymorphism in modulating cardiac autonomic function.
1] Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan [2] Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Chuan-Chia
CC
Chang
Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Wen-Hui
WH
Fang
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Hsin-An
HA
Chang
1] Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan [2] Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
San-Yuan
SY
Huang
D000328:Adult; D000483:Alleles; D002681:China; D003710:Demography; D003865:Major Depressive Disorder / Q000235:genetics* / Q000473:pathology; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D012737:Sex Factors; D014630:Vagus Nerve / Q000502:physiology
D017475:Receptors, Nerve Growth Factor