The Molecular Epidemiology Research Of Susceptibility Genes Of Alzheimer’s Disease In Northern Chinese Population

Objection To investigate the molecular epidemiological characteristics of the variabilityof the eight genes associated withAlzheimer’s disease in Northern Chinese population.Methods By literature search and analysis of bioinformatics research, the part of theAlzheimer’s disease (AD) susceptibility loci of Europe and Japan identified as a candidateSNPs replicated in Beijing population, selecting12SNPs in8genes, which were CR1(rs3818361, rs6656401), SORCS3(rs10786828, rs7894737), FRMD4A (rs2446581),KCNMA1(rs16934131), SORL1(rs6589885, rs3781834), PICALM (rs10792832, rs561655),NTF3(rs6332), AR (rs139374285). Through designing a case-control, using PCR-HRMtechnology for genotyping and sequencing combined genotyping results,12SNPs weregenotyped in250AD patients and438normal controls selected from the Beijing population.Compare each SNP genotype and allele frequencies between cases and controls, thedistribution of genotypes in different genetic models to determine the mutation sites mayassociate with AD in Beijing population. By producting cumulative effects analysis andgeneralized multifactor dimensionality reduction (GMDR) analysis were to understand thegenetic epidemiology etiology of AD. Stratified by ApoE gene loci associated with eachgenotype was related to its danger.Results1) The allele and genotype distribution of CR1SNP rs3818361between casesand control groups were significantly different (P=0.007，OR=1.374，95%CI:1.090-1.733;P=2.3×10-6) G allele frequency distribution in the case group was significantly higher than thedistribution of frequencies in the control group. Genetic analysis of the model, recessive and the ultra-dominant genetic models between the case and control groups were significantlydifferent (P=4.9×10-6, OR=2.123，95%CI:1.533-2.940; P=4.6×10-7, OR=0.444，95%CI:0.323-0.611); Additive genetic model was also significantly different (P=0.003, OR=1.492，95%CI:1.149-1.937)；Co-dominant model AG/AA there was significant difference betweenthe two groups (P=0.018, OR=0.522，95%CI:0.302-0.901)。2) The allele and genotype distributions of SORCS3SNP rs7894737between the case andcontrol groups were significantly different (P=0.011，OR=1.470，95%CI：1.091-1.980；P=9.4×10-5). Genetic analysis in the model, the recessive between cases and controls hassignificant difference (P=1.8×10-5, OR=12.84，95%CI:2.893-56.970), Additive geneticmodel was also significantly different(P=0.011, OR=1.474，95%CI:1.091-1.990); Co-dominantgenetic model CC/AA had significant difference between two groups (P=1.6×10-5,OR=13.09，95%CI:2.941-58.29), CC frequency was significantly higher than the controlcases.3) The allele and genotype distributions of AR SNP rs139374285between the case andcontrol groups were significantly different (P=0.001，OR=2.542，95%CI：1.406-4.597；P=0.037). Dominant and recessive genetic models between the two groups were significantlydifferent (P=0.010, OR=3.708，95%CI:1.275-10.779； P=0.043， OR=2.076，95%CI:1.010-4.268); Additive genetic model was also significantly different(P=0.037, OR=1.576，95%CI:1.027-2.420)；Co-dominant genetic model TT/CC had significant difference betweentwo groups(P=0.010, OR=3.707，95%CI:1.275-10.779).4) The group of previous work ApoE SNP rs429358allele and genotype distributionbetween cases and control groups were significantly different (P=1.2×10-9，OR=3.516，95%CI：2.302-5.369；P=3.4×10-8). Dominant, recessive and ultra-dominant genetic modelsbetween the two groups were significantly different (P=8.0×10-9, OR=3.796，95%CI:2.374-6.069；P=0.004, OR=6.656，95%CI:1.504-29.45；P=1.8×10-6, OR=3.154，95%CI:1.942-5.122); Additive genetic model was also significantly different (P=4.2×10-8， OR=3.296，95%CI：2.152-5.048)； Co-dominant genetic model CC/TT was significantdifference (P=0.001, OR=8.783，95%CI:1.977-39.02); Co-dominant genetic model CT/TTalso had significant difference(P=3.2×10-7, OR=3.426，95%CI:2.104-5.580).5) The cumulative effect of the risk genotype showed: with the increasing number ofdangerous genotype, OR value was increasing, that the greater the number of genotypescontaining dangerous, the greater an individual’s risk ofAD.6) Used to analyze the interaction of CR1, SORCS3and AR by GMDR, the resultsshowed: There were not obvious interactions between them in models (P>0.05).7）ApoE SNP rs429358CC+CT and TT genotypes were stratified analysis, Onlyfound in three associated loci SORCS3rs7894737without carrying the ApoE gene rs429358Callele CC/CA+AAhad significant difference(P=0.048, OR=8.295，95%CI:1.009-68.20).Conclusions1) CR1rs3818361, SORCS3rs7894737and AR gene rs139374285may besusceptible to AD risk loci;2) The greater the number of risk genotypes carried by thepatient, the greater an individual’s risk of AD;3) Interaction between AR, CR1and SORCS3showed these were not effect of gene-gene’s interactions.