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Original Research

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

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Pages 1369-1375 | Published online: 20 Nov 2019
 

Abstract

Background

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 3ʹ-untranslated region with risk and outcome of ischemic stroke in a Chinese Han population.

Methods

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.

Results

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 3ʹ-UTR containing the mutated allele C changed luciferase activity when compared to co-transfection with BDNF 3ʹ-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.

Conclusion

Our study demonstrates that the SNP rs7124442 in BDNF 3ʹ-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.

Acknowledgment

This work was supported by the Natural Science Foundation Program of WuXi Health and Family Planning Commission (NO. Q201616).

Disclosure

The authors report no conflicts of interest in this work.