Association of the brain-derived neurotrophic factor Val66Met polymorphism with body mass index, fasting glucose levels and lipid status in adolescents

Abstract

Brain-derived neurotrophic factor (BDNF) has an important role in energy balance. It suppresses food intake, reduces hepatic glucose production and converts white fat into brown fat in adipose tissue, leading to energy dissipation, lowered blood glucose and a lean phenotype. Studies have shown that the single nucleotide polymorphism (SNP) Val66Met within BDNF may be associated with obesity, insulin sensitivity, type 2 diabetes mellitus (T2DM) and dyslipidemia. The objective of the study was to investigate the association of the Val66Met polymorphism with body mass index (BMI), fasting glucose levels and lipid profile in Serbian adolescents. The study included 308 randomly selected healthy adolescents, 153 (49.68%) boys and 155 girls (50.32%), 15 years of age. Data including age, gender, height, weight, lipid profile and fasting glucose were recorded. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. No association of this polymorphism was found with BMI and lipid profile. However, significant association was observed between this polymorphism and fasting blood glucose (FBG). Carriers of a Val/Val genotype had significantly higher mean values of fasting glucose level compared to carriers of Val/ Met and Met/Met genotypes (p = 0.01). To confirm these results multiple linear regression analysis was performed. Body mass index and gender were taken as covariates. Carriers of the Val/Val genotype had significantly higher levels of FBG (β = -0.152, p = 0.02). A statistically significant association between BMI and glucose level was also observed (β = 0.124,p = 0.033). This polymorphism could be associated with fasting glucose level in Serbian adolescents, thus further research would be of great interest to validate these results.

Associations of the BDNF Val66Met Polymorphism With Body Composition, Cardiometabolic Risk Factors, and Energy Intake in Youth With Obesity: Findings From the HEARTY Study

“…Although all participants in our study were living with overweight or obesity, our findings that the BDNF polymorphism could not differentiate carriers of Val vs. Met variants on BMI is consistent with studies that included youth with and without obesity from Spain ( Arija et al, 2010 ), Mexico ( León-Mimila et al, 2013 ) and Serbia ( Vidovic et al, 2020 ). Similarly, Friedel et al (2005) reported that no differences in BDNF allele frequency were observed in German children and youth with severe obesity, underweight students, and normal weight controls.…”

“…It is noteworthy, however, that the Val66Met polymorphism is highly conserved and the Val66 prodomain BDNF ligand has been shown to reduce dendritic spine density in hippocampal neurons and facilitates long-term hippocampal depression (Guo et al, 2016), an effect that is blunted by the Met prodomain BDNF (Mizui et al, 2016). This highlights that the Met66 prodomain ligand may confer selective advantages to hippocampal structure and plasticity, which may also explain, in part, findings that the Met-allele carriers have exhibited lower cardiometabolic disease risk in children (Kalenda et al, 2018;Vidovic et al, 2020), lower BMI in healthy adults (Sustar et al, 2016), and fewer CVD events and milder CVD severity in adult cardiac patients (Jiang et al, 2017).…”

“…The so-called hypofunctioning Met allele was positively associated with BMI in a large sample of human adults ( Shugart et al, 2009 ) and children ( Skledar et al, 2012 ; Martínez-Ezquerro et al, 2017 ), but other studies reported no associations in adults ( Friedel et al, 2005 ) and children ( Arija et al, 2010 ; Vidovic et al, 2020 ). Moreover, other studies have found opposite results, whereby the Met allele was associated with lower BMI in healthy adults ( Sustar et al, 2016 ), adolescents ( Kalenda et al, 2018 ), and lower fasting ( Vidovic et al, 2020 ) and post-prandial glucose levels ( Kalenda et al, 2018 ). Similarly, there is some evidence, albeit limited, to suggest that the minor Met allele is associated with increased caloric intake in children ( Kalenda et al, 2018 ), but stronger evidence to suggest that the Met allele is associated with disordered eating, such as binge-eating ( Gratacòs et al, 2007 ), consistent with animal research showing BDNF suppression is associated with hyperphagia ( Kernie et al, 2000 ).…”

“…Thus, the Met allele has been identified as a hypofunctional BDNF allele, whereas the Val allele is associated with normal packaging and expression of BDNF. The so-called hypofunctioning Met allele was positively associated with BMI in a large sample of human adults (Shugart et al, 2009) and children (Skledar et al, 2012;Martínez-Ezquerro et al, 2017), but other studies reported no associations in adults (Friedel et al, 2005) and children (Arija et al, 2010;Vidovic et al, 2020). Moreover, other studies have found opposite results, whereby the Met allele was associated with lower BMI in healthy adults (Sustar et al, 2016), adolescents (Kalenda et al, 2018), and lower fasting (Vidovic et al, 2020) and post-prandial glucose levels (Kalenda et al, 2018).…”

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.…”