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

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.

Interaction between dietary total antioxidant capacity and BDNF Val66Met polymorphism on lipid profiles and atherogenic indices among diabetic patients

“…However, some authors have suggested the Met-allele carriers have lower risk for obesity, postprandial glucose and HbA1c levels 25 , 44 , 45 . Additionally, also some studies have observed no association with anthropometric indices and lipid profile 46 – 48 . The inconsistent results have been revealed on the association between the Val66Met polymorphism and obesity and lipid profile, proposing that environmental factors like dietary intake may be modify this association.…”

Moderating Effects of BDNF Genetic Variants and Smoking on Cognition in PTSD Veterans

“…This lack of difference in BMI (and BMI categories) was also confirmed in our previous study including a smaller number of veterans with PTSD, veterans without PTSD, and a large number (more than 1500) of healthy control population-based sample [ 76 ]. In addition, BMI values did not differ significantly between 316 veterans with PTSD, subdivided into carriers of the BDNF rs6265 A vs. homozygous GG genotype carriers, or between the BDNF rs56164415 T vs. CC genotype carriers [ 68 ].…”

“…Genotyping of the BDNF rs6265 and BDNF rs56164415 was described in detail before [ 68 ]. Genomic DNA was isolated from peripheral blood using a salting-out method [ 69 ].…”

The interaction between brain-derived neurotrophic factor (BDNF) Val66met polymorphism and dietary indices, The Healthy Eating Index (HEI), The Diet Quality Index-International (DQI-I), and Phytochemical index (PI), on anthropometric indices, inflammatory, and oxidative stress markers in patient with type2 diabetes

“…The human BDNF gene, extending over 70 kb, is located on chromosome 11, region p13-14. There are hundreds of common single-nucleotide polymorphisms (SNPs) in the BDNF gene (9). Val66Met polymorphism (rs6265) is a common and functional SNP which results in a valine (Val) to methionine (Met) substitution at codon 66 (8,9).…”

“…There are hundreds of common single-nucleotide polymorphisms (SNPs) in the BDNF gene (9). Val66Met polymorphism (rs6265) is a common and functional SNP which results in a valine (Val) to methionine (Met) substitution at codon 66 (8,9). Many studies show that BDNF can be related to eating behavior, food intake and modulation of the secretion of insulin, leptin, ghrelin, and pro in ammatory cytokines.…”