**Background:** Childhood obesity is a global public health crisis. Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in energy homeostasis, appetite, and cardiovascular regulation. Previous studies on BDNF levels and BDNF gene polymorphisms (G196A and C270T) in relation to obesity have yielded conflicting results, and data in Thai children were lacking.
**Methods:** This observational case-control study included 469 Thai children aged 8–12 years (190 obese, 279 nonobese) recruited from public schools in Bangkok between June 2019 and January 2021. Anthropometric measurements (weight, height, WC, BMI, BMI z-score) and blood pressure were obtained. Fasting blood samples were collected after a 12-hour fast. Plasma BDNF was measured by ELISA (intra-assay error <5%, interassay <9%). Glucose and lipid profiles (TC, HDL-C, LDL-C, TG) were measured enzymatically; non-HDL-C and TyG index were calculated. Hematological parameters (RBC, WBC, platelet counts) were determined. Genotyping of BDNF G196A (rs6265) and C270T (rs56164415) was performed using PCR-RFLP. Statistical analyses included t-tests, Mann-Whitney U-tests, chi-square tests, Pearson's correlation, binary logistic regression, and two-way ANOVA.
**Key Results:** Obese children had significantly higher weight, BMI, BMI z-score, WC, systolic BP (113.0 vs. 100.0 mmHg), diastolic BP (71.4 vs. 63.2 mmHg), glucose (88.7 vs. 86.2 mg/dL), TG (80.0 vs. 60.0 mg/dL), non-HDL-C (138.0 vs. 131.0 mg/dL), TyG index (8.3 vs. 8.0), and WBC count (8.1 vs. 6.4 ×10⁹/L), and significantly lower HDL-C (46.0 vs. 56.0 mg/dL) (all p<0.01). Plasma BDNF levels did not differ significantly between nonobese (32.2±6.4 ng/mL) and obese (33.8±6.4 ng/mL) groups (p=0.079). Two-way ANOVA showed no effect of gender, obesity, or their interaction on BDNF levels. BDNF was positively correlated with systolic BP (r=0.185, p<0.01), diastolic BP (r=0.128, p<0.05), TG (r=0.158, p<0.05), TyG index (r=0.186, p<0.01), RBC count (r=0.198, p<0.01), WBC count (r=0.242, p<0.01), and platelet count (r=0.383, p<0.01). Logistic regression showed the BDNF G196A polymorphism was significantly associated with decreased systolic BP (OR=0.984, 95% CI: 0.971–0.998, p=0.020) after adjusting for gender and age. No significant associations were found between C270T and any parameter. Genotypic and allelic distributions of both polymorphisms did not differ between obese and nonobese groups. In a multivariable logistic regression model for obesity, TyG index (OR=3.113, p=0.009), glucose (OR=1.088, p=0.005), and WBC count (OR=1.064, p<0.001) were significant independent predictors. The Hosmer-Lemeshow test indicated good model fit (χ²=11.7, p=0.189).
**Clinical Implications:** This study found that obesity in Thai children is associated with a clustering of cardiometabolic risk factors but not with altered plasma BDNF levels or the two BDNF polymorphisms studied. The positive correlation between BDNF and cardiometabolic risk factors (BP, TG, TyG index, WBC) suggests BDNF may be involved in cardiovascular and metabolic regulation, potentially through inflammatory pathways. The association of the BDNF G196A polymorphism with lower systolic BP suggests a possible protective role of the A allele against hypertension in children, though this remains preliminary. The TyG index, glucose, and WBC count were strong independent predictors of obesity, highlighting their potential utility as screening markers. Limitations include the relatively small sample size for genotyping, lack of direct body fat assessment, and absence of data on diet, lifestyle, and family history. Further research with larger sample sizes and broader genetic analysis is needed to confirm these findings.