Abstract
A rapid increase in obesity prevalence has been observed in Pakistan. Multiple genetic and environmental factors disrupt energy homeostasis and increase body weight. BDNF regulates energy homeostasis, body mass index, and lipid parameters. Polymorphism of BDNF Val66Met rs6265 can disrupt energy homeostasis and alter BMI and lipid parameters. The primary goal of this study was to investigate the association of BDNF rs6265 with anthropometric and lipid profiles in obese Pakistani subjects and to evaluate the binding affinity of wild and mutant BDNF protein with tropomyosin receptor kinase B (TrkB). This case-control study was conducted in the Pakistani population aged 20-59 years. A total of 66 obese and 66 control subjects were included. A total of 2 ml whole peripheral blood was collected. Genotyping analysis of variation in BDNF (rs6265) was determined by using PCR-RFLP. In-silico analysis of wild and mutant BDNF protein and TrkB was blind-docked with ClusPro. SPSS was used for the statistical analysis. Obese attributes had significantly greater neck circumference, body fat percentage, and lower high-density lipoprotein, as compared to healthy individuals (P<0.05). A significant association was observed between genotypic variation rs6265 and hip circumference, waist circumference, BMI, body fat percentage, and cholesterol (P<0.05). The AA genotype in obese subjects had the highest count contributing 56% of the obese samples, followed by GG, having a frequency of 44%. There was also a significant difference in both allelic and genotypic frequencies between the obese and normal subjects (P<0.05). BDNF rs6265 genotypes showed a significant association between obesity and its attributes. Docking results showed that the rs6265 polymorphism in BDNF reduced the binding affinity between BDNF and TrkB. These findings highlight the complex role of genetic factors in obesity and suggest that future studies may help inform personalized treatment approaches.
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