Functional BDNF rs7124442 Variant Regulated by miR-922 is Associated with Better Short-Term Recovery of Ischemic...

Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin, which contributes to the neuronal survival and synaptic plasticity. This study investigated the associations of BDNF polymorphisms at the 3'-untranslated region with risk and outcome of ischemic stroke in a Chinese Han population.

500 patients and 520 controls were enrolled for BDNF rs7124442 genotyping. The binding of miR-922 to BDNF rs7124442 was examined by luciferase assay; BDNF expression was assessed using qRT-PCR.

Alcohol consumption, cigarette smoking, diabetes, hypertension (all P < 0.001) and higher serum triglycerides concentration (P = 0.009) were associated with an increased risk of developing ischemic stroke. After adjusted for age and sex, logistic regression analysis showed that IS patients harbored with rs7124442 TC genotype had a milder initial stroke (Dominant model: OR = 0.45, 95% CI = 0.25-0.81, P = 0.015), and also showed a better short-term recovery (Dominant model: OR = 0.39, 95% CI =0.24-0.68, P = 0.003). Furthermore, we found that co-transfection of hsa-miR-922 mimics with BDNF 3'-UTR containing the mutated allele C changed luciferase activity when compared to co-transfection with BDNF 3'-UTR containing the wild-type allele. Besides, patients carrying BDNF rs712444 TC or CC genotype had an increased level of BDNF compared with patients with the TT genotype.

Our study demonstrates that the SNP rs7124442 in BDNF 3'-UTR, through affecting the regulatory role of miR-922 in BDNF expression, might act as a protective factor for the outcome of patients with ischemic stroke.