Table_1_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.DOCX

BackgroundBrain-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).
MethodsPsychometric, 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.
ResultsThe 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.
ConclusionThis 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.

背景：脑源性神经营养因子（Brain-derived neurotrophic factor, BDNF）是一种神经递质调节剂，在神经元存活与生长中发挥关键作用，参与神经元可塑性调控，因此对于学习、记忆与认知发育至关重要。此外，其在食欲、体重与代谢调控中同样不可或缺，并在心血管系统中扮演核心角色。BDNF基因的Val66Met多态性（rs6265）会导致BDNF分泌减少，并与认知损伤、能量稳态异常及心血管事件相关。本研究旨在同时评估BDNF基因rs6265多态性与三项量化表型的关联，即智商（intelligence quotient, IQ）、体重指数（body mass index, BMI）与血压（blood pressure, BP）。
方法：本研究收集了全部246名受试者的心理测量学、人体测量学与生理测量学数据。采用WASI-II INDIA量表评估认知能力。针对rs6265多态性（C196T），通过等位基因特异性PCR进行基因分型并确定基因型。统计分析采用MS-Excel与SigmaPlot软件，以p<0.05作为显著性阈值。使用带有95%置信区间的比值比模型检验关联效应，所采用的遗传模型包括共显性、隐性、显性、超显性与加性模型。
结果：等位基因C与T的频率分别为72%与28%。在显性遗传模型下，次要等位基因T与更低的平均言语理解指数（比值比=2.216，p=0.003，95%置信区间=1.33–3.69）、更低的平均操作推理指数（比值比=2.634，p<0.001，95%置信区间=1.573–4.41）以及更低的平均全量表智商-4（比值比=3.159，p<0.001，95%置信区间=1.873–5.328）存在显著的易感关联。携带Met等位基因的受试者体重指数升高（比值比=2.538，p<0.001，95%置信区间=1.507–4.275），收缩压与舒张压均降低（收缩压：比值比=2.051，p=0.012，95%置信区间=1.202–3.502；舒张压：比值比=2.162，p=0.006，95%置信区间=1.278–3.657）。在隐性遗传模型下，同样检测到T等位基因携带者的智商与血压出现多倍下降，而体重指数升高。
结论：此项创新性研究有助于加深对该表型相关遗传改变的认知，可为临床医师与研究人员探究该神经营养因子的诊断与预后价值提供参考。