Raspodjela genotipova moždanoga neurotrofnoga čimbenika (BDNF Val66Met) i razina N-glikana u plazmi kao pokazatelji prekomjerne tjelesne mase u djece Distribution of the brain derived neurographic factor (BDNF) genotypes and plasma N-glycans levels as predictors of overweight in children

摘要

Overweight and obesity are growing health-care problems worldwide. Environmental factors contribute to calory intake and consumption and therefore influence the prevalence of overweight and obesity; however family studies show that heritage affects increased body weight and obesity in up to 55-85% of cases. One of the genetic factors that has an important role in food intake regulation, feeding behavior and control of body mass index (BMI) is brain-derived neurotrophic factor (BDNF). BDNF Val66Met polymorphism is associated with various eating disorders and changes in BMI, resulting in malnutrition or obesity. N-glycosilation is closely associated with adipogenesis and diabetes mellitus induced by obesity. Structural changes in N-glycans, with consequent increased or decreased enzimatic activities, impact feeding, and are associated with overweight and obesity. The highest plasma values of N-glycans are perceived in early childhood, and these values decrease with aging. The aim of this study was to determine, in 93 healthy children 6-7 old, selected from the narrow demographic area and of the same ethnic background, the association between the BDNF Val66Met polymorphism and overweight and obesity, and changes in certain structural variants of N-glycans between overweight and obese children compared to normal weight children, subdivided according to the national referral criteria for BMI in boys and girls. Our results confirmed the association between BDNF Val66Met polymorphism and overweight and obesity. Namely, there were significant differences in the frequency of the BDNF genotypes (p=0,016), alelles (p=0,011) and Met carriers (the combined Met/Met and Met/Val genotype) and Val/Val homozygotes (p=0,009) between children with normal weight, overweight and obese children. Increased proportion of the Met alelle in overweight children compared to normal weight children contributed to this significance. In addition, we have found significant differences in N-glycan levels between the groups of children with normal weight and obese groups. In obese and overweight children, increased levels of N-glycans, specifically triantennary and tetraantennary, as well as trigalactosylated, tetragalactosylated, trisialylated and tetrasialylated N-glycans were found, while levels of biantennary, monosialylated biantennary, digalactosylated and monosialylated forms were decreased compared to children with normal weight. The results confirmed our hypothesis of the more frequent presence of the BDNF Val66Met Met allele in overweight and obese children compared to normal weight children, and the association between significant number of N-glycan forms and obesity. These results offer the opportunity to define easy obtainable peripheral biochemical and genetic biomarkers of obesity and overweight, with aim to prevent obesity and to implement healthy feeding habits in children.