Genetic Variants of the Brain-Derived Neurotrophic Factor and Metabolic Indices in Veterans With Posttraumatic Stress Disorder.

Lucija Tudor,Marcela Konjevod,Gordana Nedic Erjavec,Dubravka Svob Strac,Oliver Kozumplik,Matea Nikolac Perkovic,Marina Sagud,Zrnka Kovacic Petrovic,Nela Pivac,Suzana Uzun

doi:10.3389/fpsyt.2018.00637

Abstract

Posttraumatic stress disorder (PTSD) is a trauma and stressor related disorder that may develop after exposure to an event that involved the actual or possible threat of death, violence or serious injury. Its molecular underpinning is still not clear. Brain-derived neurotrophic factor (BDNF) modulates neuronal processes such as the response to stress, but also weight control, energy and glucose homeostasis. Plasma BDNF levels and a functional BDNF Val66Met (rs6265) polymorphism were reported to be associated with PTSD, as well as with increased body mass index (BMI) and dyslipidaemia in healthy subjects and patients with cardio-metabolic diseases, but these results are controversial. The other frequently studied BDNF polymorphism, C270T (rs56164415), has been associated with the development of different neuropsychiatric symptoms/disorders. As far as we are aware, there are no data on the association of BDNF Val66Met and C270T polymorphisms with metabolic indices in PTSD. Due to high rates of obesity and dyslipidaemia in PTSD, the aim of this study was to elucidate the association of BDNF Val66Met and C270T polymorphisms with BMI and lipid levels in veterans with PTSD. We hypothesized that BDNF variants contribute to susceptibility to metabolic disturbances in PTSD. The study included 333 Caucasian males with combat related PTSD, diagnosed according to DSM-5 criteria. Genotyping of the BDNF Val66Met and C270T polymorphisms was performed using the real-time PCR method. Results were analyzed using hierarchical multiple linear regression and the Mann–Whitney test, with p-value corrected to 0.005. The results showed that BDNF Val66Met and BDNF C270T polymorphisms were not significantly associated with BMI, total cholesterol, LDL-cholesterol, HDL-cholesterol or triglycerides. Although the BDNF C270T polymorphism was nominally associated only with HDL-cholesterol in veterans with PTSD, this significance disappeared after controlling for the effect of age. Namely, slightly higher plasma HDL values in T allele carriers, compared to CC homozygotes, were associated with differences in age. Our results, controlled for the critical covariates, revealed that BDNF Val66Met and C270T were not significantly associated with metabolic indices in veterans with PTSD and that these genetic variants do not contribute to susceptibility to metabolic disturbances in PTSD.

Highlights

Posttraumatic Stress DisorderPosttraumatic stress disorder (PTSD) is a trauma- and stressorrelated disorder [1] that develops in some, but not all individuals exposed to death, threatened death, actual or threatened serious injury, or actual or threatened sexual violence
Due to the high rates of both obesity and dyslipidaemia in Posttraumatic Stress DisorderPosttraumatic stress disorder (PTSD), the aim of this study was to elucidate the association of brain-derived neurotrophic factor (BDNF) Val66Met and BDNF C270T polymorphisms with body mass index (BMI) and lipid levels in veterans with PTSD
After removal of the outliers for each metabolic parameter, there were N = 294 participants for HDL, N = 316 for BMI; N = 315 for cholesterol, N = 311 for LDL and N = 303 for triglycerides, respectively

Summary

Introduction

Posttraumatic Stress DisorderPosttraumatic stress disorder (PTSD) is a trauma- and stressorrelated disorder [1] that develops in some, but not all individuals exposed to death, threatened death, actual or threatened serious injury, or actual or threatened sexual violence. Metabolic complications and components of the metabolic syndrome are associated with increased body mass index (BMI) values or weight gain, and with other clusters of physiological, biochemical, clinical, and metabolic factors that strongly increase the risk of type 2 diabetes and different cardiovascular diseases [6]. These metabolic abnormalities include central obesity measured as waist circumference, dyslipidaemia (reduced HDL levels and increased triglyceride levels), high blood pressure, insulin resistance, as well as raised fasting plasma glucose. People with a sedentary life style, who do not exercise, consume a high fat diet and develop these metabolic abnormalities, have increased risk for cardiovascular and metabolic disorders [6]

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