Association of BDNF gene missense polymorphism rs6265 (Val66Met) with three quantitative traits, namely, intelligence quotient, body mass index, and blood pressure: A genetic association analysis from North India

Abstract

Background: Brain-derived neurotrophic factor (BDNF), a neurotransmitter modulator, plays a significant role in neuronal survival and growth and participates in neuronal plasticity, thus being essential for learning, memory, and the development of cognition. Additionally, it is crucial for appetite, weight, and metabolic control and plays a pivotal role in the cardiovascular system. The Val66Met polymorphism (rs6265) of the BDNF gene causes a decrease in BDNF secretion and plays a role in impairments in cognition, energy homeostasis, and cardiovascular events. The present study aimed to evaluate the association of polymorphism (rs6265) of the BDNF gene with three quantitative traits simultaneously, namely, intelligence quotient (IQ), body mass index (BMI), and blood pressure (BP). Methods: Psychometric, morphometric, and physiometric data of the total participants (N = 246) were collected. WASI-IIINDIA was used to measure cognitive ability. Genotyping was carried out using allele-specific PCR for the rs6265 polymorphism (C196T), and genotypes were determined. Statistical analyses were performed at p < 0.05 significance level using MS-Excel and SigmaPlot. The odds ratio models with a 95% confidence interval were used to test the associations. The used models are co-dominant, recessive, dominant, over–dominant, and additive. Results: The allelic frequencies of alleles C and T were 72 and 28%, respectively. Under the dominant genetic model, a significant susceptible association of minor allele T was observed with a lower average verbal comprehensive index (OR = 2.216, p = 0.003, CI (95%) =1.33–3.69), a lower average performance reasoning index (OR = 2.634, p < 0.001, CI (95%) = 1.573–4.41), and a lower average full-scale IQ-4 (OR = 3.159, p < 0.001, CI (95%) = 1.873–5.328). Carriers of Met-alleles were found to have an increased body mass index (OR = 2.538, p < 0.001, CI (95%) = 1.507–4.275), decreased systolic blood pressure (OR = 2.051, p = 0.012, CI (95%) = 1.202–3.502), and decreased diastolic blood pressure (OR = 2.162, p = 0.006, CI (95%) = 1.278–3.657). Under the recessive genetic model, several folds decrease in IQ and BP and an increase in BMI with the presence of the T allele was also detected. Conclusion: This novel study may improve our understanding of genetic alterations to the traits and hence be helpful for clinicians and researchers to investigate the diagnostic and prognostic value of this neurotrophic factor.