Study On The Relationship Between Vitamin D Metabolism Pathway Gene Polymorphism And Post-stroke Depression

Objective:The purpose of this study was to investigate whether the genetic polymorphisms of the vitamin D(VitD)metabolic pathway are associated with post-stroke depression(PSD),in order to find the genetic susceptibility loci of PSD and provide new clues for early identification of PSD and exploration of genetic pathogenesis.Methods:This study included stroke patients who were hospitalized in the Department of Neurology,Xiangya Hospital,Central South University from July 2019 to August 2021 with onset within 14 days.We collected the time of onset,length of hospital stay,age,sex,years of education,smoking and drinking history,hyperlipidemia,hypertension,diabetes,coronary heart disease,TOAST classification,stroke area,endovascular treatment and so on.The severity of Stroke was assessed by the National Institutes of Health Stroke Scale(NIHSS)and Barthel Index(BI).Finally,patients were assessed as PSD or non-post-stroke depression(NPSD)based on the Diagnostic and Statistical Manual of Mental Disorders(DSM-5).Meanwhile,we used Hamilton Depression Scale-17(HAMD-17)to evaluate the degree of depression in PSD patients.We used SNPscan typing techniques to detect the VDR rs11568820、rs1544410、rs2228570、rs7975232、rs731236、GC rs4588、rs2298849、rs1155563、rs4752、CYP2R1 rs12794714、rs10741657、rs7129781、CYP24A1 rs2296241、rs2248137、rs2248359、rs2762939、rs2296239、rs2274133、CYP27B1 rs10877012 in subjects,and then used statistical analysis to screen for factors associated with PSD.Results:A total of 246 patients were enrolled in this study,of which 128(52.03%)were judged to be PSD,mainly manifested as mild depressive disorder(82.03% of the PSD group).Univariate statistical analysis showed that age,gender,BMI,years of education,smoking,drinking,diabetes,hyperlipidemia,hypertension,endovascular treatment,work nature,BI index,m RS score were not significantly different between PSD group and NPSD group(P>0.05).There were significant differences in the history of coronary heart disease,NIHSS and MMSE scores between the two groups(P<0.05).The incidence of PSD in cerebral infarction patients with different TOAST types was statistically significant(χ2=0.019,P=0.000).In patients with cerebral infarction,the anterior circulation,posterior circulation,and different stroke regions involved in the anterior and posterior circulations were statistically significant between the PSD group and the NPSD group(χ2=5.773,P=0.016).Univariate analysis showed that among the 19 related loci of VitD metabolic pathway genes,the genotype frequency of rs4588 and rs4752 of GC gene was different between PSD group and NPSD group(χ2=7.538,P=0.023;χ2 =176.354,P=0.000).The genotype distribution and allele distribution frequency of other SNP loci of VDR gene,GC gene,CYP2R1 gene,CYP24A1 gene and CYP27B1 gene were not statistically significant.Multivariate logistic regression analysis showed that the prevalence of coronary heart disease(P=0.012,95%CI=1.172-3.715),NIHSS score(P=0.041,95%CI=1.006-1.299),MMSE score in PSD group(P=0.013,95%CI=0.861-0.982)was statistically significant compared with NPSD group,while age,sex,hyperlipidemia,hypertension,diabetes,endovascular treatment,stroke area,BI,m RS,GC gene rs4588,rs4752 genotypes and alleles were not statistically significant between the PSD group and the NPSD group(P>0.05).Conclusion:We found that history of coronary heart disease,higher NIHSS score and lower MMSE score,TOAST type of cerebral infarction,GC gene rs4588 and rs4752 loci may be associated with PSD.