| Background and Aims: The post stroke depression(PSD),a common compliment of brain stroke,is characterized by neuropsychiatric impairment such as depressed mood,generalized anxiety,and apathy,which has been the most serious factor causing low quality of life in stroke patients,and increases death risk of brain stroke.Therefore,it is very important to elucidate the pathologenesis and development mechanism of PSD.Recently,increasing evidence has shown that the development of PSD is associated with individualls' s genetic susceptivity which may correlate with the damage repair capacity of neuron cells.Here we specifically conducted a molecular epidemiological research to investigate whether polymorphisms at apolipoprotein E(APOE)codon 130(rs429358,allele from C to T,the corresponding amino acid from Cysteine to Arginine)and codon176(rs7412,allele from C to T,the corresponding amino acid from Arginine to Cysteine)modify the risk of PSD,and to accumulate epidemiological evidence of PSD prevention and therapy.Methods: This study is a hospital-based case-control study.All subjects,including 76 brain infarction cases with PSDThe diagnosis of PSD was based on Chinese classification and diagnostic criteria of mental disorders,Third Edition(CCMD-?).Hamilton Depression Scale-24(HAMD-24)was used to determine the degree of depression.88 cases with brain infarction diagnosed through the Guidelines for diagnosis and treatment of acute ischemic stroke in China [2010],and 109 healthy controls without any genetic susceptibility evidence and the family history of depression,are from Guangxi Region.To control possible confounders,three groups were frequently matched based gender,on age,and race.Taq Man-MGB-PCR and Gene sequencingwere used to assess the mutations of APOE gene;while the brain function were analyzed using the regional resting-state cerebral blood flow(r CBF)which was tested by a Siemens Symbia T2 SPECT/CT Dual Head System.The risk relationship between APOE polymorphisms and PSD was evaluated by logistic regression model with odd ratios(OR)and 95% confidence interval(CI).Results:(1)In this study,a total of 164 cases with brain infarction were included in final analysis,and 76 patients were ultimately diagnosed as cases with PSD,with a 46.3% of incidence.(2)Analysis of the APOE rs429358 and rs7412 polymorphisms revealed the genotype distribution of control individuals was consistent with predictions from the Hardy-Weinberg equilibrium(P>0.05).(3)There were not significantly different distributions of APOE rs7412 genotypes and alleles among PSD group,NPSD group,and healthy control group(P> 0.05).(4)The frequencies of genotypes with APOE rs459358 C alleles(also called rs429358 TC/CC)among patients with PSD were higher than among cases with brain infarction but not PSD,or among healthy controls.The corresponding values were 47.4% vs.20.5% vs.22.0%,respectively,with significant P value(P< 0.05).(5)The results from multivariable logistic regression exhibited that the C alleles of APOE rs429358 increased the risk of PSD with risk values of 3.39(1.90-6.05)for PSD group vs NPSD group,3.21(1.88-5.45)for PSD group vs.healthy control group,and 3.28(2.07-5.22)for PSD group vs.NPSD group plus healthy control group,respectively.Furthermore,this increasing risk was modified by the number of APOE rs429358 risk alleles.Compared to those without risk alleles,these inviduals with one risk allele featured 3.17(1.42-7.05)-time risk of PSD;whereas risk would be 11.24(2.98-42.40)when under the conditions of two risk alleles.(6)The APOE rs429358 genotypes affected the levels of serum glcouse and total cholesterol(7.03±3.40 m M and 6.87±3.05 m M for rs429358-TC/CC,5.35±0.84 m M and 5.29±2.49 m M for rs429358-TT,respectivly).(7)The APOE rs429358 genotypes were significantly related to the degrees of PSD(P< 0.05).(8)The different distributions of r CBF were observed between right and left lobes of cerebrum where lower r CBF value among left temporal and parietal lobe(P< 0.05).However,similar results did not be found among NPSD cases.(9)The APOE rs429358 genotypes significantly modified the r CBF values.These individuals with rs429358-TT had a higher r CBF value than those with rs429358-TC/CC(0.74±0.15 vs.0.67±0.16,P< 0.05).Interestingly,the r CBF of bilateral brain did show any difference among these inviduals with rs429358-TT;whereas significant difference was observed among those with rs429358-TC/CC(r CBF value: left temporal and parietal lobe more than right temporal and parietal lobe).Conclusion: These results suggest that the rs429358 polymorphism in APOE gene should increase PSD risk and this increasing risk may correlate with the r CBF. |
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