Potential unfavorable impacts of BDNF Val66Met polymorphisms on metabolic risks in average population in a longevous area

Abstract

BackgroundBrain-derived neurotrophic factor (BDNF) has been implicated in cognitive performance and the modulation of several metabolic parameters in some disease models, but its potential roles in successful aging remain unclear. We herein sought to define the putative correlation between BDNF Val66Met and several metabolic risk factors including BMI, blood pressure, fasting plasma glucose (FPG) and lipid levels in a long-lived population inhabiting Hongshui River Basin in Guangxi.MethodsBDNF Val66Met was typed by ARMS-PCR for 487 Zhuang long-lived individuals (age ≥ 90, long-lived group, LG), 593 of their offspring (age 60–77, offspring group, OG) and 582 ethnic-matched healthy controls (aged 60–75, control group, CG) from Hongshui River Basin. The correlations of genotypes with metabolic risks were then determined.ResultsAs a result, no statistical difference was observed on the distribution of allelic and genotypic frequencies of BDNF Val66Met among the three groups (all P > 0.05) except that AA genotype was dramatically higher in females than in males of CG. The HDL-C level of A allele (GA/AA genotype) carriers was profoundly lower than was non-A (GG genotype) carriers in the total population and the CG (P = 0.009 and 0.006, respectively), which maintained in females, hyperglycemic and normolipidemic subgroup of CG after stratification by gender, BMI, glucose and lipid status. Furthermore, allele A carriers, with a higher systolic blood pressure, exhibited 1.63 folds higher risk than non-A carriers to be overweight in CG (OR = 1.63, 95% CI: 1.05 - 2.55, P = 0.012). Multiple regression analysis displayed that the TC level of LG reversely associated with BDNF Val66Met genotype.ConclusionsThese data suggested that BDNF 66Met may play unfavorable roles in blood pressure and lipid profiles in the general population in Hongshui River area which might in part underscore their poorer survivorship versus the successful aging individuals and their offspring.Electronic supplementary materialThe online version of this article (doi:10.1186/s12877-016-0393-0) contains supplementary material, which is available to authorized users.

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

“…In children and adolescents from the general population, the BDNF Val66Met polymorphism was not associated with any of the lipid indices ( 97 ). In contrast to our study and cited ( 63 , 97 ) findings, the presence of one or two A alleles of the BDNF Val66Met was significantly associated with lower HDL cholesterol levels and higher risk for obesity in old and very old Chinese healthy subjects ( 95 ). In that particular study subjects carrying the A allele had elevated triglyceride levels, but reduced HDL cholesterol levels compared to the GG genotype carriers ( 95 ).…”

“…In contrast to our study and cited ( 63 , 97 ) findings, the presence of one or two A alleles of the BDNF Val66Met was significantly associated with lower HDL cholesterol levels and higher risk for obesity in old and very old Chinese healthy subjects ( 95 ). In that particular study subjects carrying the A allele had elevated triglyceride levels, but reduced HDL cholesterol levels compared to the GG genotype carriers ( 95 ). The differences between studies are in the diagnosis (PTSD vs. normal controls) and in the age of included subjects (i.e., Peng's study included three groups: age ≥90; age 60–77; and age 60–75, while our veterans were on average 56 years old).…”

“…As there are no such data in the literature, we might presume that this study is the first to show no association of BDNF Val66Met variants with BMI in combat veterans with PTSD. In line with our data, BMI was not significantly different in A carriers compared to GG genotype carriers of the BDNF Val66Met in elderly healthy Chinese subjects ( 95 ), or in elderly healthy individuals who were followed longitudinally ( 71 ). However, there are conflicting results in the literature regarding this polymorphism and BMI in control subjects.…”

“…A recent meta-analysis confirmed only one BDNF SNP, rs925946, significantly related to obesity and BMI in large groups of healthy subjects ( 98 ). Discrepancies in the results could be explained by the different diagnostic groups (PTSD vs. controls), ethnic background ( 19 , 99 , 100 ), age, gender, living environment, diet, lifestyle, and smoking ( 95 ). Since recently a strong LD between BDNF rs6265 and rs10501087 was reported, suggesting that these two SNPs are dependent genetic markers associated with BMI ( 98 ), in future studies this BDNF SNP, rs10501087, should be also evaluated.…”

Inhibition of the CD36 receptor reduces visceral fat accumulation and improves insulin resistance in obese mice carrying the BDNF-Val66Met variant

“…The variant commonly occurs with high frequency in humans, and association of the met allele with a higher body mass index implied potential involvement of the variant in obesity (25,36). Use of mice with the human BDNF val66met knock-in in both alleles (BDNF…”