| Objective: Alzheimer's disease(AD)is a progressive neurodegenerative disease that interacts with multiple genes.We conducted a pilot study to explore the single nucleotide polymorphisms(SNPs)of five AD-related genes,including the Anterior Pharynx defective-1(APH1B),the human prion protein gene(PRNP),3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR),Silencing Information Regulatory Factor 2 Homologue 1(SIRT1)and apolipoprotein E(APOE)with the Xinjiang Han Chinese Alzheimer.At the same time,we attempted to determine whether the Bcl-2-related X protein(BAX)promoter methylation and the APOE promoter methylation were associated with Xinjiang Han AD.Methods: We selected the elderly in the hospital cadres(old age medicine)and aged over 60 years old in our hospital from 2014 to 2015.All the People who were surveyed were diagnosed by the experienced elderly medical department and neurologist according to the DSM-IV standard.17 cases of AD patients as a case group(including 7 males and 10 females),the average age of 75.65 ± 5.86 years;from the same period of hospitalized patients,select the age,gender,ethnicity,education,etc.to match the normal old age 34 cases of the control group(including 17 males and 17females),the average age of 77.59 ± 7.41 years old.SNP genotyping of six loci related to AD,including APH1 B rs1047552,PRNP rs1799990,HMGCR rs3846662,SIRT1rs7895833,APOE rs7412 and rs429358 were performed by Sanger sequencing.The genetic polymorphisms were compared with those of Xinjiang Han nationality Alzheimer's disease relationship.The DNA methylation level of APOE and BAX genes was determined by real-time quantitative PCR(QMSP)technique,and the relationship between methylation and Alzheimer's disease in Xinjiang was compared.Results:(1)Theresults showed that APOE rs7412 and rs429358 were significantly correlated with AD(?2 = 9.718,P = 0.002).There was no significant difference between APH1 B rs1047552,PRNP rs1799990,HMGCR rs3846662 and SIRT1 rs7895833 gene polymorphism in case group and control group(P> 0.05).(2)There was no significant difference in APH1 B rs1047552,PRNP rs1799990,HMGCR rs3846662 and SIRT1 rs7895833 gene polymorphisms between the two groups according to whether to carry APOE?4 layered(P> 0.05).(3)The methylation level of BAX promoter in AD patients was significantly lower than that in the control group(t =-2.078,P = 0.045),and the level of BAX methylation in female AD patients was lower than that in the control group(t =-2.230,P =0.046).According to whether or not to carry APOE?4 stratification,in the case and the control group were not found between the statistical significance(P> 0.05).(4)There was no significant difference in the methylation level of APOE promoter between the case group and the control group(P> 0.05),and further stratified by sex,no significant difference was found.The methylation level of AD patients with APOE ? 4 gene was higher(p = 0.025).(5)In the case and control group,no age was found to be related to APOE and BAX methylation(P> 0.05).The APOE and BAX methylation levels were not correlated with age(P> 0.05).Conclusion:(1)The polymorphisms of APOE rs7412 and rs429358 were associated with the presence of AD in Xinjiang,suggesting that APOE rs7412 and the expression of APOE rs7412 and rs429358 were found in the six SNPs(APH1B rs1047552,PRNP rs1799990,HMGCR rs3846662,SIRT1 rs7895833,APOE rs7412 and rs429358)rs429358 may be one of the risk factors for AD.(2)The methylation level of BAX gene promoter in the case group was lower than that in the control group,especially in women,suggesting that lower methylation of BAX promoter may be one of the risk factors of AD in Xinjiang Han nationality in woman.(3)The APOE methylation level of APOE ? 4 genotype in AD patients was significantly higher,suggesting that APOE?4 may have a certain effect on methylation level in AD patients. |
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