| Purpose:1.Deepen the data mining of the syndrome rule of aMCI based on latent class analysis method,improve the aMCI's syndrome differentiation system and make use of its clinical syndromes to make beneficial explorations,explore the connection among aMCI syndromes,lipid metabolism and related protein genes.Provides some references for the objectification of aMCI TCM syndrome differentiation.2.2.To study the serum levels of aMCI lipid and lipid metabolism pathway related proteins(Apo lipoprotein E,Cholesterylester transfer protein Low-density lipoprotein Receptor,Adenosine Triphosphate Binding Cassette Transporter 7 and serum markers?Microtubule associated protein,Phosphorylated microtubul,and leves of beta amyloid 1-42,beta amyloid 1-40?beta-Amyloid 1-40,Abeta 1-40??.Then to search for lipids Metabolic association with aMCI onset,cognitive function and serum markers.3.To study the genotype and allelic distribution of rs sites of ApoE??2??3??4?,CETP?I405V and TaqIB?,LDLR?rs688,rs5925?,ABCA7?rs3752246?in Han Chinese aMCI population in Liaoning,thus to explore its relevance to aMCI and cognitive function.4.To investigate the relationship between TCM syndromes of aMCI and serum lipid-related protein,gene polymorphisms and aMCI serum markers,and provide some references for aMCI TCM syndrome differentiation.Material and method:1.According to the principle of case-control study,600 cases of permanent Han subjects were collected in 2 tertiary hospitals and 6 old-age care centers in Shenyang City,of which 300 were in the aMCI group,and their cognition was normal with age,gender,and disease history.Group 300 cases.General clinical data collection,history collection,and neuropsychiatric scale testing were performed on all patients.Through a questionnaire survey of the fourChinese medicines for the 300 aMCI subjects who meet the requirements,through the data analysis method of inductive potential category syndromes law of aMCI,thus find out the six major aMCI optimization and stable card type.2.Using ELISA method to detect all patients serum ApoE,ABCA7,LDLR,CETP and Tau,P-Tau,1 to 40 A beta,A beta 1-42 protein levels,and observe the correlation of aMCI lipid metabolism pathway related protein expression with aMCI?onset,cognitive function,serum markers?.3.Obtained the information and sequence of ApoE,ABCA7,LDLR and CETP through the Gen Bank of the national biological information center.IMDL method is used to detect the genotype of ApoE aMCI patients blood??2??3??4?,CETP?I405V and TaqIB?,LDLR?rs688 and rs5925?,ABCA7?rs3752246 rs115550680?,using SPSS statistical analysis software ApoE,CETP,LDLR,ABCA7 SNPs in the Shenyang han aMCI genotype and allele distribution features of the crowd,and to explore its correlation with the onset and cognitive function of aMCI and serum markers..4.To explore the relationship among aMCI TCM syndrome types,blood lipid metabolism and the SNPs of ApoE??2??3??4??CETP?I405V,TaqIB?,LDLR?rs688,rs5925?,ABCA7?rs3752246?further analysis in patients with aMCI ApoE,,CETP,LDLR,ABCA7 gene polymorphism and main symptoms of TCM and the relationship between the syndrome classification.Results:1.The level of education in the aMCI group was lower than that in the cognitive normal group(*P<0.05,**P<0.01),and the degree of smoking and alcohol consumption were higher than in the cognitive normal group(*P<0.05,**P<0.01).The scores of depression and life ability were both lower than those of cognitively normal old people(*P<0.05,**P<0.01).2..According to the analysis of TCM syndromes,the top 15 symptoms in patients with aMCI were:forgetfulness,diminished intelligence,unresponsiveness,dizziness,fatigue,weak knees,miscalculation,fatigue,urinary frequency,dry stool,and chest tightness,tinnitus,shortness of breath,upset and dry mouth.The tongue veins ranked in 5 are:red tongue,thin white fur,greasy fur,slippery pulse and narrow pulse string.After latent variable category clusteranalysis,six categories were found,corresponding to liver and kidney deficiency syndrome,liver qi stagnation syndrome,turbid phlegm and phlegm syndrome,spleen and kidney yang deficiency syndrome,heart and spleen deficiency syndrome,and kidney essence deficiency syndrome.After the clustering,the syndromes were distributed in order of composition ratio:liver and kidney deficiency syndromes,heart and spleen deficiency syndromes,phlegm and Mongolian syndromes,liver qi stagnation syndromes,and deficiency of spleen and kidney yang syndrome and kidney essence deficiency certificate.3.The proportion of patients with hypercholesterolemia and high-low-density lipoproteinemia in aMCI patients was significantly higher than that in cognitive normal patients(**P<0.01).The levels of TC and LDL in aMCI patients were significantly higher than those in cognitive normal patients,however HDL was lower than those in cognitive normal patients.In the cognitive normal group,the difference was statistically significant(*P<0.05,**P<0.01).After adjusting for confounding factors,it was concluded by regression analysis that TC was an independent risk factor for the development of aMCI?OR=1.998,95%CI=1.015-3.934,P=0.045?.And the serum levels of TC and LDL-C were negatively correlated with the MMSE score of patients with aMCI?*P<0.05?,there was a positive correlation between serum levels of HDL-C and MMSE scores of aMCI patients?P<0.05?.The level and proportion of ApoE?LDLR?CETP?ABCA7 in aMCI group were significantly lower than those in non-cognitive dysfunction group(*P<0.05,**P<0.01).After adjusting for confounding factors,regression analysis showed that serum ApoE was an independent protective factor for the pathogenesis of aMCI?OR=0.662,95%CI=0.489-0.896,P=0.008?.The serum level of ApoE was positively correlated with MMSE score of aMCI patients?*P<0.05?.4.The result of orrelation analysis between aMCI serum markers and lipids and lipid metabolism pathway proteins:The levels of serum P-tau in the aMCI group were significantly higher than those in the normal group?*P<0.05?.After adjusting for the confounding factors,the results of regression analysis showed that P-tau was associated with the onset of aMCI?OR=1.003,95%CI=1.000-1.006,P=0.038?,and has negative correlation with MMSE scale scores,the level of HDL,and ApoE?*P<0.05?.P-tau has positive correlation with the level of TC and LDL?*P<0.05?.When the sensitivity and specificity of the diagnostic value of P-tau and P-tau was measured by ROC curve method,it was found that P-tau has a certain significance for the diagnostic value of aMCI?*P<0.05?.The levels of serum A?1-42 in the aMCI group were significantly higher than those in the normal group?*P<0.05?.After adjusting for the confounding factors,the results of regression analysis showed that A?1-42 was associated with the onset of aMCI?OR=1.021,95%CI=0.994-1.049,P=0.025?.and has negative correlation with MMSE scale scores,the level of ApoE and LDLR?*P<0.05?.A?1-42 has positive correlation with the level of TC and LDL?*P<0.05?.When the sensitivity and specificity of the diagnostic value of P-tau and P-tau was measured by ROC curve method,it was found that A?1-42 has a certain significance for the diagnostic value of aMCI?*P<0.05?.The levels of serum A?1-40 in the aMCI group were significantly lower than those in the normal group?*P<0.05?,After adjusting for the confounding factors,the results of regression analysis showed that A?1-40 was associated with the onset of aMCI?OR=0.436,95%CI=0.378-0.494,P=0.007?,and has negative correlation with the level of LDL?*P<0.05?.A?1-40 has positive correlation with the level of ABCA7,ApoE and LDLR.?*P<0.05?.When the sensitivity and specificity of the diagnostic value of A?1-40 was measured by ROC curve method,it was found that P-tau has no certain significance for the diagnostic value of aMCI?*P<0.05?.5.The result of relation analysis of genetic polymorphisms of lipid metabolism pathway related protein with aMCI and cognitive function:There was a statistical differences between the two groups in ApoE gene polymorphisms(**P<0.01).The?2/2 and?4/4 genotype frequencies were significantly different between the aMCI group and the cognitive normal group(**P<0.01),and the?4 allele frequency was significantly higher in the aMCI group than in the control group?16.00%vs.9.67%?,?2allele frequency was significantly lower than the cognitive normal group?5.33%vs8.50%?.The two-class regression analysis of two groups of lipid metabolism-related protein gene polymorphisms aMCI can be obtained,?4 allele is aMCI susceptible allele?OR=1.525,95%CI=0.981-2.369,P=0.041?,The carrier incidence rate was 1.525 times that of non-?4 carriers,while the carrying?4/4 homozygote was aMCI susceptibility genotype?OR=3.707,95%CI=1.796-7.649,P=0.000?,The incidence of carrier aMCI was 3.707 times that of non-?4/4carriers.The?2 genotype was the protective allele of aMCI?OR=0.596,95%CI=0.374-0.948,P=0.029?.The incidence of aMCI in patients carrying?2 was 0.596 times higher than that of non-?2 carriers,and carrying?2 genotype was the protective allele of aMCI?OR=0.596,95%CI=0.374-0.948,P=0.029?,and the incidence of?2/2 carrier aMCI was 0.699 times that of non-?2/2 carriers.Compared with non-?4 individuals,?4 carriers are more likely to have cognitive decline,mainly reflected in the carrying?4 allele There was a correlation with MMSE scores,immediate recall,and language ability?*P<0.1?.The carrying of?4/4 allele was associated with immediate recall,attention and calculation,and language ability?*P<0.1?.There was no statistical differences between the two groups in CETP gene polymorphisms?P>0.05?.And There was no statistical differences with aMCI,MMSE neither.There was a statistical differences between the two groups in LDLR gene polymorphisms?*P<0.05?.The frequency of CC genotype of aMCI group rs688 was higher than that of cognitive normal group?72.67%vs 78.33%?,the frequency of TT genotype was lower than that of cognitive normal group?4.67%vs1.33%?;frequency of C allele in aMCI group was low In the cognitively normal group?84.00%vs 88.50%?,the T allele frequency was higher than the cognitive normal group?16.00%vs 11.50%?.The two-class regression analysis of two groups of lipid metabolism-related protein gene polymorphisms aMCI can be obtained that the LDLR rs688 TT genotype was a susceptibility genotype of aMCI?OR=1.506,95%CI=1.374-1.948,P=0.029?.The incidence of aMCI in carriers was 1.506 times that of non-TT carriers,while the carrying T allele is a susceptible allele of aMCI?OR=1.399,95%CI=0.477-1.625,P=0.047?,and the incidence of carriers was 1.399 times that of non-T carriers.6.The difference in LDLR,rs688 gene polymorphism between the two groups was statistically significant?*P<0.05?.The frequency of CC genotype of aMCI group rs688 was higher than that of cognitive normal group?72.67%vs 78.33%?,the frequency of TT genotype was lower than that of cognitive normal group?4.67%vs1.33%?;frequency of C allele in aMCI group was low In the cognitively normal group?84.00%vs 88.50%?,the T allele frequency was higher than the cognitive normal group?16.00%vs 11.50%?.The ABCA7 gene rs3752246gene polymorphism was statistically different between the two groups??2=6.108,P=0.047?.The frequency of CC allele in aMCI was significantly higher than that in the cognitive normal group?48.00%vs39.00%?.The frequency of GG allele was significantly lower than that of the cognitive normal group?8.67%vs13.00%?.The frequency of C allele was higher than that of cognitive normal group?69.67%vs 63.00%?,and the frequency of G allele was lower than that of cognitive normal group?30.33%vs 37.00%?.LDLR rs688 gene polymorphism is associated with cognitive function.The rs688 locus TT genotype of LDLR is negatively correlated with immediate recall and language ability?*P<0.1?.The T allele is negatively correlated with immediate recall.?*P<0.1?.The level of TC in the liver-kidney deficiency syndrome was the lowest(*P<0.05,**P<0.01),and the level of A?1-42 was the highest(*P<0.05,**P<0.01).There was no significant difference from the syndrome of orifices confused by phlegm?P>0.05?,and had no significant difference with other syndromes?P>0.05?.The levels of TC in heart and spleen deficiency syndrome were higher than those in liver and kidney deficiency?*P<0.05?.The level of A?1-42 was lower than that in the syndrome of orifices confused by phlegm(??P<0.01).There was no significant difference between other indicators and other syndromes?P>0.05?.The TC level in the syndrome of orifices confused by phlegm was the highest(?P<0.05,??P<0.01),and there was no difference between heart and spleen deficiency syndrome?P>0.05?.The HDL level was the lowest,and there was a difference with the spleen and kidney yang deficiency,heart and spleen deficiency syndrome(?P<0.05,??P<0.01).The level of A?1-42 was the highest and there was no statistical difference between liver and kidney deficiency syndrome(**P<0.01,?P<0.05).There was no significant difference between other indicators and other syndromes?P>0.05?.The serum levels of ApoE,LDLR,CETP,and ABCA7 were not significantly different among different syndromes of aMCI?P>0.05?.7.The distribution of ApoE,CETP,LDLR,ABCA7 genotypes and alleles in different syndromes was different(*P<0.05,**P<0.01).Further correlation analysis shows that,There was a positive correlation between ApoE?4/4and?2/2 genotypes and liver and kidney deficiency syndrome?*P<0.1?,2.2 and 1.402 times of other syndromes,?2 allele and liver and kidney deficiency syndrome and spleen and kidney yang,respectively.There was a positive correlation between deficiency syndromes?*P<0.05?,1.63 and 1.39 times that of other syndromes,and there was a positive correlation between?4 allele and liver and kidney deficiency syndrome?*P<0.05?.Other syndromes were present.1.856 times,there is no significant correlation between the remaining.The V/V genotype of CETPI405V was positively correlated with heart and spleen deficiency?*P<0.1?,2.264 times that of other syndromes;there was a positive correlation between I allele and liver and kidney deficiency syndrome?*P<0.1?was 1.817 times that of other syndromes;TaqIB B1 allele was associated with liver and kidney deficiency syndrome?*P<0.1?,which was 1.729 times that of other syndromes.There was a positive correlation between LDLRrs688 TT genotype and Yimeng Qingjing syndrome?*P<0.1?,which was 2.029 times that of other syndromes.There was a positive correlation between the C allele of ABCA7rs3752246 and spleen-kidney yang deficiency?*P<0.1?,which was 2.111 times that of other syndromes.Conclusion:1.The disorder of lipid metabolism may aggravate the cognitive impairment in the elderly,and TC is an independent risk factor for aMCI.2.The increase of serum P-tau,A?1-42,and decrease of A?1-40 are early warning signals of early aMCI,which may be a substitute for cerebrospinal fluid as a new early recognition marker,and Serum levels of P-tau and A?1-42 have some value in the diagnosis of aMCI.3.ApoE,CETP,and LDLR gene polymorphisms are related to TCM syndrome types.ApoE?4/4 and?2/2 genotypes may increase the risk of liver and kidney deficiency,and?2 and?4 alleles may increase liver and kidney deficiencies and spleen and kidneys.The risk ofYang deficiency;CETPI405V I allele,TaqIB B1,LDLRrs688 T,LDLR rs5925T allele alleles can increase the risk of liver and kidney deficiency syndrome.Therefore,the ApoE?4/4,?2/2 genotypes,ApoE?4,?2,CETP TaqIB B1,LDLRrs688 T alleles can be used as a reference index for the dialectical classification of liver-kidney deficiency syndrome.The LDLRrs688C allele can be used as a reference for heart and spleen deficiency syndromes.index.4.We can optimize the classification of the Chinese medicine syndromes of aMCI by using latent variable category analysis technology.There are 6 optimized types which are liver and kidney deficiency syndrome,heart and spleen deficiency syndrome,turbid phlegm syndrome,liver qi stagnation syndrome,spleen and kidney yang Deficiency syndrome,kidney essence deficiency certificate.The abnormal blood lipids in the.aMCI Yimeng Qingyao syndrome and heart and spleen deficiency syndrome are obvious,mainly due to metabolic abnormalities of TC and HDL.Lipid protein gene polymorphisms can guide the aMCI syndrome differentiation of TCM syndromes.The main manifestations are ApoE?4/4,?2/2 genotype,ApoE?4,?2,CETPI405V I,CETP TaqIB B1 alleles can be used as dialectical classification of liver and kidney deficiency syndrome.The reference index,CETPI405V V/V genotype can be used as a reference index of heart and spleen deficiency syndrome.The ApoE?2,ABCA7 rs3752246C allele is a reference index for syndrome differentiation of spleen and kidney yang deficiency,LDLRrs688 TT genotype is a Syndrome reference classification indicators.The blood lipid metabolism related protein serum level has no reference value for aMCI syndrome differentiation. |
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