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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.

Functional Ser205Leu polymorphism of the nerve growth factor receptor (NGFR) gene is associated with vagal autonomic dysregulation in humans