The Association Of MME MicroRNA Binding Site Polymorphism With Risk Of Late Onset Alzheimer's Disease In Northern Han Chinese

Objective: Our study aim to investigate the potential risk of common locus rs6665 with LOAD in Northern Han Chinese population,which was screened from the specially relative sequence within the targeted gene NEP(MME)of 3'UTR mi RNA-187.Methods: By the large sample study,we recruited 984 patients with LOAD as the case group from Qingdao Municipal Hospital and other several public hospital in Shandong province,1354 healthy people were selected as control group from the examination center of Qingdao Municipal Hospital and other severally cooperative hospitals,elderly Centers.The DNA samples were extracted from peripheral blood of all subjects.Through the " Biological information science " approach,we screened the rs6665 from the special sequence within MME gene,which was targeted by mi RNA-187.Five screening criterions have been identified to complete the screening aim.Through the custom-by-design 2-×48-Plex SNP scan TM kit(Cat#: G0104 K,Genesky Biotechnologies Inc.,Shanghai,China),the SNP rs6665's genotyping was obtained.The produced technology about SNP genotyping for kit was exclusively belongs to Genesky Biotechnologies Inc.Furthermore,this technology was built on the double ligation polymerase chain reaction(PCR-LDR)and multiplex fluorescent.APOE genotype was achieved by the approach that was reported by Donohoe et al.The frequencies of both allele and genotype were assessed by counting.The distributional difference of Genotype and allele were also compared by chi-square test in the two groups.Basing on different APOE ?4 status,we further stratified the two individual groups,and examined the possible distinction of the two relative subgroups by the chi-square test.The possible correlation between the minimum C allele of MME gene SNP rs6665 and the risk of AD onset was analyzed by logistic regression method,which was simultaneously adjusted by age,gender and APOE ?4 status under totally three genetic models that were individually named dominant,recessive and additive.The P value,odds ratios(OR)and 95% confidence intervals(95% CI)were all calculated to each genetic model.Moreover,we tested the possible interactions between SNP rs6665 with APOE ?4 allele by logistic regression adjusted by age and gender in every model.All the statistical analyses werecarried out by SPSS 19.0 software.All the analyses defined P<0.05 as the level of significant difference.Result: The Callele was discovered and identified as the lower frequencies allele in both group,comparing the higher allele A.The genotypic distributions of MME SNP rs6665(P=0.003)and allele A/C(P=0.001)had significant difference between the two groups(OR=1.255,95% CI =1.102-1.429).Furthermore,we stratified the two groups(LOAD patients and control subjects)by APOE?4 status(carrier or non-carrier).Ether in the APOE?4 allele carriers(APOE?4+)or in the APOE?4 allele non-carriers(APOE?4-)subgroup,the significant differences of genotype distributer have been found between the LOAD patients and controls: APOE ?4+:genotype P=0.014;APOE?4-: genotype P=0.013;In addition,without any significance in allele distributer:APOE?4+:P=0.597;APOE ?4-:P=0.549.After adjusting age,gender and APOE?4 status of logistic regression analysis,the minor C allele of rs6665 was documented performing a significantly risk relationship between the LOAD onset in all three genotypic models(Dominant: P=0.003,OR=1.291,95%CI=1.092-1.526;Recessive: P=0.030,OR=1.425,95%CI=1.035-1.961;Additive: P=0.001,R=1.249,95%CI=1.093-1.427).In the dominant genetic model,we further found the significant interaction between SNP rs6665 with APOE?4 allele by logistic regression adjusted by age and gender(P=0.035,OR=1.569,95%CI=1.031-2.386).After stratifying in the dominant genotype model by APOE?4 status,MME SNP rs6665 was still found as the risk site to LOAD onset in the APOE?4 carriers(P=0.002,OR=1.846,95%CI=1.264-2.697).Conclusions: Our study firstly confirmed the association of MME SNP rs6665 with LOAD onset.And this SNP site in the specially targeted sequence of MME gene by the 3'UTR mi RNA-187.This SNP was further confirmed as a risk factor to LOAD patients.Moreover,we found the significant interaction between SNP rs6665 with APOE?4 allele on LOAD onset.