The Influence of Val66Met Polymorphism in Brain-Derived Neurotrophic Factor on Stroke Recovery Outcome: A Systematic Review and Meta-analysis

Abstract

Background and purpose. A single nucleotide polymorphism at nucleotide 196 (G/A) in the human brain-derived neurotrophic factor ( BDNF) gene produces an amino acid substitution (valine to methionine) at codon 66(Val66Met). It is unclear whether carriers of this substitution may have worse functional outcomes after stroke. We aimed to explore the distribution of Val66Met polymorphism and evaluate the effect of different genotypes on stroke functional recovery. Methods. Several databases were searched using the keywords BDNF or brain-derived neurotrophic factor, codon66, G196A, rs6265, or Val66Met, and stroke. Results. A total of 25 articles were relevant to estimate the distribution of alleles; 5 reports were applied in the meta-analysis to assess genetic differences on recovery outcomes. The genetic model analysis showed that the recessive model should be used; we combined data for AA versus GA+GG (GG—Val/Val, GA—Val/Met, AA—Met/Met). The results showed that stroke patients with AA might have worse recovery outcomes than those with GA+GG (odds ratio = 1.90; 95% CI: 1.17-3.10; P = .010; I2 = 69.2%). Overall, the A allele may be more common in Asian patients (48.6%; 95% CI: 45.8%-51.4%, I2 = 54.2%) than Caucasian patients (29.8%; 95% CI: 7.5%-52.1%; I2 = 99.1%). However, in Caucasian patients, the frequency of the A allele in Iranians (87.9%; 95% CI: 83.4%-92.3%) was quite higher than that in other Caucasians (18.7%; 95% CI: 16.6%-20.9%; I2 = 0.00%). Conclusion. Val66Met AA carriers may have worse rehabilitation outcomes than GA+GG carriers. Further studies are needed to determine the effect of Val66Met polymorphism on stroke recovery and to evaluate this relationship with ethnicity, sex, age, stroke type, observe duration, stroke severity, injury location, and therapies.

Genetic and Neurophysiological Biomarkers of Neuroplasticity Inform Post-Stroke Language Recovery

“…Notably, our findings are consistent with our mechanistic hypothesis: because Val 66 Val carriers show stronger propensity for neuroplastic change than Val 66 Met carriers, 12,35 they will be more likely to recover and present with mild aphasia. Our results are also consistent with a meta-analysis and multiple independent reports that BDNF polymorphism influenced general stroke recovery, 43 as well as post-stroke motor 44 and functional recovery, 45 such that Val 66 Met carriers demonstrate worse rehabilitation outcomes than Val 66 Val carriers.…”

Genetic and neurophysiological biomarkers of neuroplasticity inform post-stroke language recovery

“…Notably, our findings are consistent with our mechanistic hypothesis: because Val 66 Val carriers show stronger propensity for neuroplastic change than Met allele carriers [12,44], they will be more likely to recover and present with mild aphasia. Our results are also consistent with a meta-analysis and multiple independent reports that BDNF polymorphism influenced general stroke recovery [52], as well as post-stroke motor [53] and functional recovery [54], such that Met allele carriers demonstrate worse rehabilitation outcomes [55,56]. This indicates that genetic effects may have a stronger influence on cognition when neural resources are reduced, as in old age [56].…”

Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association

“…In a review of 5 articles on the role of the single nucleotide polymorphism (G/A) at nucleotide 196 in the human brain-derived neurotrophic factor ( BDNF ) gene, which produces an amino acid substitution (valine to methionine) at codon 66 (Val66Met), patients with stroke with the AA genotype had worse recovery outcomes than those with GA+GG genotypes (OR, 1.90 [95% CI, 1.17–3.10]; I 2 =69.2%). 266 Overall, the A allele may be more common in Asian patients than White patients.…”