The BDNF Val66Met polymorphism is associated with lower BMI, lower postprandial glucose levels and elevated carbohydrate intake in children and adolescents

Background: The amino acid-changing exonic variant rs6265 (Val66Met polymorphism) in the brain-derived neurotrophic factor (BDNF) has been linked to obesity in several genotype-phenotype association studies.

Objective: To identify metabolic factors by which this effect might be conveyed, we aimed to investigate its correlation with (i) obesity, (ii) metabolic parameters, (iii) serum levels of BDNF and (iv) measures of energy intake in children and adolescents.

Methods: We genotyped the variant in 2131 subjects (age 6-18 years) and checked for an association with obesity. Secondly, we correlated the genotype with parameters of glucose and lipid metabolism (fasting/postprandial glucose and insulin levels, HbA1c, homeostasis model assessment, Matsuda, high-density lipoprotein, low-density lipoprotein, total cholesterol and triglycerides) in a smaller subset of 845 subjects. We determined BDNF serum levels in 177 individuals by enzyme-linked immunosorbent assay and assessed the association with genotype and metabolic parameters. Finally, we investigated the association between genotype and macronutrient intake from self-reported food diaries (n = 146).

Results: The minor Met allele was associated with lower BMI standard deviation score (p = 0.002). Post-pubertal Met allele carriers showed lower postprandial glucose levels and a lower HbA1c (β = 0.15, p = 0.046 and β = 0.27, p = 0.012, respectively). Neither the genotype nor any of the metabolic parameters correlated with BDNF serum levels. We observed an increased total calorie intake (β = -0.21, p = 0.007) with increased carbohydrate and protein intake (β = -0.22, p = 0.005 and β = -0.14, p = 0.028, respectively) in Met allele carriers.

Conclusions: We confirmed the association of the minor Met allele with lower BMI in children and provide new data that it is associated with lower postprandial glucose in post-pubertal subjects. Moreover, Met allele carriers reported to consume more carbohydrates and proteins.