Association Of Serum Levels Of Brain-derived Neurotrophic Factor And Polymorphisms With Vascular Cognitive Impairment

Objective: Brain-derived neurotrophic factor ( BDNF ) has been implicated in the development of the nervous system (namely, neuronal growth, differentiation, synaptic connectivity) and in neuronal survival and repair, BDNF may play a key role in the activity dependent modulation of synapses and has therefore been implicated in long-term potentiation, a form of synaptic plasticity associated with memory formation. Animal experimental evidence has suggested that BDNF levels and high-affinity receptor TrkB mRNA are increased expressed after cerebral ischemia. However, little is known about in vivo BDNF in VCI patients. The BDNF gene is localized to the boundary of chromosome 11p13. A single nucleotide polymorphism (SNP)G→A in the BDNF gene that causes a valine to methionine substitution at codon 66 ( Val66Met ) has been demonstrated to affect human memory and hippocampal function. To our knowledge, there are no reports of any association between VCI and the BDNF polymorphism G196A or C270T. The aim of the present study is to examine the serum levels of BDNF and polymorphisms G196A and C270T in vascular cognitive impairment. Methods: 42 patients of VCI were chosen from 2008 Mar to 2008 Oct, including 20 patients of mild VCI,14 of moderate VCI and 8 of sever VCI. 49 cerebral infarct patiens with no dementia were selected. 46 controls were chosen simultaneously in health examinated people. Enzyme-linked immunosorbant assay (ELISA) was used to measure the serum levels of BDNF. The genotypes and allele frequencies of G196A and C270T were analyzed by PCR-restriction fragment length polymorphi- sm(PCR -RLFP).Analyze clinical data to search risk factors to vascular cognitive impairment.Results:1 gender, age, BMI, level of education, blood-fat or fasting blood-glucose showed no significantly difference between any two groups; hypertension showed significantly difference between VCI group and NC group ( p<0.05 ) and also NDCI group vs NC group ( p<0.05 ); case history of stroke showed significantly difference between VCI group and NC group (p<0.05 ) and also NDCI group vs NC group ( p<0.05 ).2 BDNF serum levels proved not to be normally distributed(skewness=1.459,kurtosis=0.738);The mean score ( 28.869 ) of BDNF levels in VCI group was lower than in NDCI group ( 40.132 ), and there showed significantly difference (χ2=7.303, p<0.05 );The mean score ( 27.000 ) of BDNF levels in VCI group was lower than in NC group ( 36.063 ), but there showed no significantly difference (χ2= 3.338, p>0.05 );The mean score ( 17.895 ) of BDNF levels in NDCI group was lower than in NC group( 18.125 ) , but there showed no significantly difference (χ2=0.004, p>0.05 ).3 In VCI subgroup, The median of BDNF levels were 56.468 ( 38.642-188.441 ), 69.177 ( 32.013- 349.513), 102.860 ( 8.108-560.445 )pg/mL respectively in mild VCI subgroup, moderate VCI subgroup and sever VCI subgroup, there showed no significantly difference (χ2=1.508,p>0.05 ).4 The levels of BDNF were not related with MMSE score, gender, age, BMI or the level of education in VCI subgroup or VCI+NDCI subgroup or NC subgroup ( P>0.05 ).5 G/A genotype was most in G196A BDNF SNP. G/A geno- type frequncies were 50.0%,63.3%,63.0% in VCI group, NDCI group, NC group respectiely,without statistical significance (χ2=5.299, P>0.05 ). G allele frequncies were 65.5%, 52.0%, 55.4% in VCI group, NDCI group, NC group respectiely,with- out statistical significance (χ2=3.534 , P>0.05 ). G196A polymorphisim genotype distributions in all of the three groups correspond to Hardy-Weinberg equilibrium , with groups'representation.6 In C270T BDNF SNP , all of the genotypes were C/C genotypes in VCI group, NDCI group and NC group. And all of the alleles were C alleles in three groups , T allele was not found. No significant differences were demonstrated in C270T BDNF genotype or allele frequencies among VCI group, NDCI group and NC group (χ2=0, P>0.05;χ2=0,P>0.05. respectively ). C270T BDNF genotype distributions in all of the three groups correspond to Hardy-Weinberg equilibrium,with groups'repre- sentation.Conclusions: 1 Case history of stroke and hypertension showed significantly difference between VCI group and control groups. Stroke and hypertension might be risk factors to vascular cognitive impairment.2 BDNF serum levels in VCI group were lower than in ND- CI group, so BDNF might play a role in pathophysiology of VCI. But BDNF serum level could not reflect the severity of VCI.3 BDNF serum levels showed no significant differences between NDCI group and normal control. BDNF might not play a role in pathophysiology of cerebral infarction.4 The levels of BDNF were not related with MMSE score, gender, age, BMI or the level of education in VCI subgroup or VCI+NDCI subgroup or NC subgroup .5 G196A or C270T BDNF genotypes or alleles showed no significant differences between any two groups,which sugges- ted that BDNF gene G196A or C270T polymorphisims might not be hereditary factors contributing to VCI.