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]

Turčić, Marijana (2015) 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]. PhD thesis, Sveučilište u Zagrebu.

PDF Download (3MB)

Abstract

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.

Abstract in Croatian

Prekomjerna tjelesna masa i pretilost predstavljaju velik javnozdravstveni problem. Okolišni čimbenici utječu na unos i potrošnju kalorija te na na pojavnost pretilosti, ali obiteljske studije pokazuju da nasljeđe utječe čak 55-85% na prekomjernu tjelesnu masu i pretilost. Jedan od genetičkih čimbenika koji ima bitnu ulogu u regulaciji unosa hrane, metabolizmu i kontroli indeksa tjelesne mase (ITM) jest moždani neurotrofni čimbenik (BDNF, engl. brain derived neurotrophic factor). Polimorfizam BDNF Val66Met povezuje se s različitim poremećajima hranjenja, te promjenama u ITM-u u vidu pothranjenosti ili pretilosti. N-glikozilacija je usko povezana s adipogenezom i šećernom bolešću provociranom debljinom. Strukturne promjene N-glikana, s posljedičnim smanjenjem ili pojačanjem enzimske aktivnosti, utječu na hranjenje i povezane su s pojavom preuhranjenosti i pretilosti. Najviše vrijednosti N-glikana u plazmi zamijećene su u ranom djetinjstvu te se njihove vrijednosti smanjuju s odrastanjem. Cilj ovog rada bio je utvrditi na 93 zdrave djece u dobi 6-7 godina iste etničke pripadnosti i uskog demografskog područja, postoji li razlika u distribuciji genotipova, alela i Met nosioca s obzirom na Val66Met polimorfizam gena BDNF između normalno uhranjene djece i djece s prekomjernom tjelesnom masom, te mijenja li se koncentracija N-glikana u normalno uhranjene djece u odnosu na djecu s prekomjernom tjelesnom masom, a temeljem nacionalnih referentnih vrijednosti centilnih krivulja ITM-a za djevojčice i dječake. Naši rezultati potvrđuju povezanost polimorfizma BDNF Val66Met i prekomjerne tjelesne mase. Naime, između normalno uhranjene i djece s prekomjernom tjelesnom masom postoji značajna razlika u distribuciji BDNF genotipova (p=0,016), alela (p=0,011) i nosioca Met alela (kombinirani Met/Met i Met/Val genotip) prema Val/Val homozigotima (p=0,009). Razlika nastaje radi povećanog udjela Met alela u skupini djece s prekomjernom tjelesnom masom u odnosu na normalno uhranjenu djecu. Također, utvrdili smo značajnu razliku u razini određenih struktura N-glikana između pretile i normalno uhranjene djece. Pronađene su povišene vrijednosti triantenarnih, tetraantenatnih, kao i trigalaktoziliranih, tetragalaktoziliranih, trisijaliziranih i tetrasijaliziranih formi, dok su vrijednosti biantenarnih, monosijaliziranih biantenarnih, digalaktoziliranih i monosijaliziranih formi N-glikana bile snižene u preuhranjene i pretile djece prema normalno uhranjenoj djeci. Navedeni rezultati potvrđuju hipotezu o većoj zastupljenosti Met alela kod djece s prekomjernom tjelesnom masom prema normalno uhranjenoj djeci, kao i povezanost značajnog broja N-glikanskih formi s prekomjernom tjelesnom masom. Ti nalazi nude mogućnost definiranja lako dostupnih perifernih biokemijskih i genetičkih pokazatelja preuhranjenosti i pretilosti, u svrhu spriječavanja pretilosti i uvođenja zdravih prehrambenih navika u djece.

Actions (login required)

View Item

Downloads