Association Analysis Of Eight Gene Variations With Alzheimer’s Disease Susceptibility In Northen Chinese Populations

Objective: To identify Alzheimer’s disease (AD) susceptibility gene In Northen Chinesepopulations, and verify its association withAD.Method:1. We examined248AD patients and408healthy controls from Beijing.Through the literature search and bioinformatic analysis, GBP2, BIN1, ADAM12, FRMD4A,SORL1, PICALM, MS4A4E, TOMM40genes, chromosome3and chromosome4variantswere screened, to investigate an association between these with AD association. Ten SNPswere genotyped by high-resolution melt and sequencing in subjects.2. Using SPSS and MDRto analysis alleles, genotype frequency and genetic models, in order to verify whethercandidate loci associated with AD risk in Northen Chinese populations and analysis theassociation of each locus genes, genotypes, genetic with AD clinical phenotype. To verify thedifferences of genotype frequency between the patients carrying APOE and the patientsnon-carriers.Results:1.3SNPs were found to be associated with AD in Northen Chinesepopulations, they were rs7081208, rs3851179and rs10119(P=0.045, P=0.032, P=0.01).(2)analysis of genetic models: AG of rs1425967was associated with AD (P=0.002, OR=0.61);CT, TT, CT+TT in rs11244841were associated with AD (P=0.032, OR=4.59; P=0.026,OR=4.68; P=0.026, OR=4.66); CT, CT+TT in rs3851179were associated with AD (P=0.01,OR=1.58; P=0.021, OR=1.49); CT, CT+TT in rs10119were associated with AD (P=0.004,OR=1.684; P=0.013, OR=1.158).3. Synergy of APOE with patients: rs11244841with CT+TT carrying ApoE gene and rs429358with CT+TT not carrying ApoE more than non carrier (P=0.003, OR=11.73)..4Degree of clinical variables dementia in patients with AD analyzed:T allele of rs2221154was significantly associated with the degree of dementia(P=0.003);codominant model of rs1425967was significantly associated with the degree of dementia(P=4.39×10-4, P=0.002); G allele and genotype GG of rs7081208and there was asignificant associated with degree of dementia (P=0.01, P=0.01); C allele and the dominantmodel with genotype CC+CT of rs720099were significantly associated with degree ofdementia (P=2.24×10-16, P=0.038).5. Gene interaction analysis: rs10119and rs3851179had an interaction relationship was significantly higher than the risk of control.6genotypecumulative effects analysis: the greater the number of risk SNP (rs7081208, rs3851179andrs10119), the more individuals suffering from AD (the value of OR from1.79to2.09to4.94)Conclusion:1. FRMD4A (rs7081208), PICALM (rs3851179) and TOMM40(rs10119)may be were AD susceptibility genes in Northen Chinese populations.2. Genotype AG ofrs1425967, genotype CT, TT, CT+TT of rs11244841may increase the risk of AD.3. CT+TT of rs429358risk genes will increase CT+TT of rs11244841effects of AD with ApoEgene.4. allele T of rs2221154, AG and GG of rs1425967, allele G and genotype GG ofrs7081208, allele C of rs720099and genotype CC+CT of the dominant model correlatedwith the degree of dementia.5. Interactions between rs10119and rs3851179would increasethe risk of AD.6. rs7081208, rs3851179and rs10119risk genotype SNPs will increase thenumber of superimposed individual’s risk for AD.6. Genotype cumulative effects analysis:the greater the number of risk SNP (rs7081208, rs3851179and rs10119), the more individualssuffering fromAD.