A Case-control Study Of The Ralated Factors Of Alzheimer's Disease In Mongolian And Han Chinese Population In Inner Mongolian Autonomous Region

Objective:To understand the characteristics of risk factors of Alzheimer's disease(AD)in Mongolian and Han population aged 65 and over in Inner Mongolia Autonomous region,to explore the distribution characteristics of risk factors of AD,to explore the changes' law of ApoE,TOMM40,PVRL2 and BIN1 genes in Mongolian sporadic AD(SAD)patients,at the same time to explore the interaction of haplotype of chromosome 19 and gene and environment.Method:1.5150 Mongolian and Han individuals aged 65 and above from 30 communities in Inner Mongolia Autonomous region were selected to investigate the risk factors of AD.2.A case-control study was used to conduct a case-control analysis of AD risk factors to evaluate the impact of related factors on AD.3.511 Mongolian patients with SAD and 392 healthy with normal cognitive function as controls were collected.The genotypes and allele frequencies of AD group and control group were analyzed by polymerase chain reaction,sequencing and case-control study.Haploid analysis and MDR method were used to study the interaction between gene and environment of Mongolian patients with SAD.Result:1.Univariate analysis showed that among Mongolian people aged 65 and over,age,sex,occupation,education,marriage,family structure,history of diabetes,history of hypertension,diastolic blood pressure,history of coronary heart disease and history of osteoarthrosis were significantly different between the two groups(P<0.05).There were significant differences in age,sex,parity,occupation,education,low income,marriage,family structure,smoking and drinking history,physical exercise,regular tea drinking,low body weight,abdominal obesity,chronic respiratory diseases,history of coronary heart disease and bone and joint disease between the two groups(P<0.05).2.(1)Gene polymorphism analysis showed that there was a significant difference in the distribution frequency of ApoE genotypes between the Mongolian SAD group and the control group(P=0.000),there was a significant difference in the distribution of ApoE 4 carrying status between the two groups(P=0.000).(2)There was significant difference of the genotypes and alleles frequencies of PVRL2 rs6857,rs6859,rs3852861,TOMM40 rs157580,rs2075650,and ApoE rs709449 in AD group and the control group(P<0.005);There was significant difference in the distribution of ApoE rs405509 genotypes and alleles frequencies between the AD group and the control group(P<0.05),but after correcting the ApoE ?4 carrier status,there was no significant difference of the genotypes and alleles frequencies distribution of the above SNPs locus in the ApoE?4 +/-group.There was no significant difference in the BIN1 rs6733839 and rs7443 73 genotypes and alleles frequency between the AD group and the control group(P>0.05).(3)haploid analysis on chromosome 19 showed that there was linkage disequilibrium among PVRL2 rs6857,TOMM40 rs157580 and 2075650,the risk of AD was lower in those with CGA haploid,but the risk of AD was higher in those with TAG,there was linkage disequilibrium among TOMM40 rs2075650,APOE rs405509 and rs769449,the risk of AD in patients with GTC haploid was lower,and the risk of AD in patients with AGT was higher.There is also a linkage imbalance among TOMM40 rs6857,rs6859 and rs157580.The risk of AD in patients with AGG is lower,and the risk of AD in patients with GTA is higher.(4)Multi-factor dimensionality reduction method was used to analyzed in the interaction between Mongolian AD gene and environment.It was found that there was interaction between ApoE ?4 and Education,TOMM40 rs157580 and BINlrs6733839,there was a significant correlation between ApoE ?4,Education and Mongolian SAD.Conclusion:1.Among Mongolian people aged 65 and above,age,sex,birth order,history of diabetes,history of hypertension,diastolic blood pressure,history of coronary heart disease and history of osteoarthrosis were risk factors for AD,while non-agricultural and animal husbandry profession,education,marriage and living with spouses and children were protective factors for AD.Age,sex,low income,multiple births,smoking,low weight,chronic respiratory diseases,coronary heart disease and bone and joint disease were risk factors in Han population.Non-agricultural and animal husbandry profession,education,marriage,living with spouse and children,regular tea drinking and exercise were protective factors of AD.2.Further verification shows that the polymorphism of ApoE gene was associated with the susceptibility to SAD in Mongolians,and that ApoE allele 4 was a risk factor for SAD in Mongolians.3.Haplotype analysis of chromosome 19 in Mongolian AD population showed for the first time that there was linkage disequilibrium among PVRL2 rs6857,TOMM40 rs157580 and 2075650,there were also linkage disequilibrium among TOMM40 rs2075650,APOE rs405509 and rs769449,and among TOMM40 rs6857,rs6859 and rs157580.Genetic polymorphisms of APOE,TOMM40,PVRL2 and BIN1 were associated with the susceptibility to SAD in Mongolian population in Inner Mongolia.4.For the first time the optimal environment-gene interaction model for the pathogenesis of Mongolian AD was constructed,that is there was a significant correlation between ApoE gene Education,TOMM40 rs157580,BIN1rs6733839 with Mongolian SAD.Multivariate Logistic regression analysis showed that there was a significant correlation between ApoE gene 4,Education with Mongolian SAD.