| Objective: The purpose of this study was to investigate the relevance of the level of DNA methylation in peripheral blood of Nuclear factor of activated B-cells signaling pathway(NF-κB)genes(ZAP70,CFLAR,CXCL2,LYN,TRADD)and the incidence of alzheimer disease and mild cognitive impairment,and detected the difference of the absolute blood telomere length(ATL)between AD,MCI and the control group.In addition,we also analyzed the correlation between peripheral blood DNA-ATL and peripheral blood DNA methylation levels,that provides a theoretical basis for further studying pathogenesis of AD and MCI.Methods: A case-control study method was used.Diagnosis was performed according to the diagnostic criteria for AD and MCI of the American Psychiatric Association of Mental Disorders Diagnostic and Statistical Manual of the revised version IV of the Alzheimer’s disease diagnostic criteria for diagnosis,and cases were screened strictly according to the inclusion and exclusion criteria.The patients aged ≥ 60 years who were admitted to the Department of Geriatrics of The First Affiliated Hospital of Xinjiang Medical University from January 2017 to May 2018 were enrolled,according to the diagnosis and exclusion criteria,there were 37 patients in AD group(20 males and 17 females),63 patients in MCI group(27 males and 36 females),and 126 normal people as control group(51 males and 75 females).First search all genes in the NF-kB signaling pathway in PubMed,keep the genes previously reported to be related to AD,then check whether these genes have CpG islands in UCSC,and then search for the above genes in CpG islands in PubMed and retain them Methylation of genes that have not been correlated with AD.Finally,the results of single-band genes wereselected by running gel experiments.ZAP70,CFLAR,CXCL2,LYN,and TRADD genes were screened by methylation Quantitative Methylation Specific PCR(qMSP)method was used to detect DNA methylation level in peripheral blood,and ATL of all samples was detected by real-time PCR(RT-PCR).Results:(1)The methylation level of ZAP70 gene in AD group was 18.450(10.430,28.760)higher than that of MCI group 2.559(1.929,3.866)(P < 0.05),and higher than that of control group 2.859(1.383,14.338)(P < 0.05),no significant difference was found between the MCI group and the control group(P >0.05);the results were consistent with the gender stratification.(2)The methylation level of CFLAR gene in AD group was 5.192(3.039,10.805)higher than that of MCI group0.718(0.441,0.894)(P < 0.05),and higher than the control group 1.104(0.391,6.558)(P< 0.05),the MCI group was lower than the control group(P < 0.05);the results were consistent with that in the male group;Among women,it was only found to be higher in the AD group than in the MCI group and the control group(P < 0.05).(3)The methylation level of CXCL2 gene in MCI group was 3.823(2.351,6.499)higher than that in AD group2.564(1.610,4.519)(P < 0.05)and higher than the control group 2.654(1.441,4.423)(P <0.05);There was no significant among the three groups in males(P > 0.05);in women,the CXCL2 gene methylation levels were higher in the MCI group than in the control group(P< 0.05).(4)There was no significant difference in methylation level of LYN gene between AD group,MCI group and control group(P > 0.05).(5)There was no significant difference in the methylation level of TRADD gene between AD group,MCI group and control group(P > 0.05).(6)MCI group ATL 0.0464(0.0456,0.0476)is shorter than the control group 0.0479(0.0463,0.0501)(P < 0.05)(P < 0.05)and shorter than AD 0.0503(0.0446,0.0543)(P < 0.05);in men,suffering from hypertension The ACI of MCI group was shorter than that of control group and AD group(P < 0.05);the ACI of MCI group was shorter than that of control group and AD group.The control group(P < 0.05);the ACI in the MCI group was shorter than that in the AD group in high school and above(P< 0.05).(7)The correlation between telomere length and methylation level of each gene was not statistically significant(P > 0.05).Conclusion:(1)Modification of DNA methylation of NF-kB signaling pathway-related genes may affect the incidence of AD and MCI.(2)ATL of peripheral blood DNA may affect the pathogenesis of AD and MCI,and there might be some mechanism for maintaining telomere length stability in AD patients.(3)DNA methylation level in peripheral blood of genes related to NF-kB signaling pathway was not found to affect the regulation of telomere length. |
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