Han Population And Three Genes Related To Alzheimer's Disease Single-nucleotide Polymorphisms Research

Genomic diversity, mainly the sing1e nucleotide po1ymorphism(SNP), is one of the most important genetic causes of inheritabledifference in disease and environmental susceptibility of humanbeing. A1zheimer's disease (AD), a devastating neurodegenerativedisorder characterized by neurofibril1ary tang1es (NFT) and seni1eplaques (SP), accounts for about 60% dementia in the wor1d. Thisdisease has been proved to be associated with SNP in several genessuch as the 6--amy1oid precursor protein (APP) gene, apolipoproteinE (AP0E) gene, preseni1in--l (PS--1) gene, presenilin--2 (PS--2) gene,al--antichymotrypsin (AACT) gene, and non--amy1oid component ofAlzheimer's disease amy1oid precursor (NACP) gene. So far, there'sst i 11 no assoc iat ion report on the endop1asmi c--ret icu 1um--assoc iatedbinding protein (ERAB) gene whose expression product contributes tothe formation of SP.Denaturant gradient gel e1ectrophoresis (DGGE) is a techno1ogythat can detect SNP at almost 100% ratio and determine theirfrequencies in comp1ex samp1es simu1taneous1y. In this paper, DGGEwaS emp1oyed to the SNP screening of three A1zheimer's diseasere18ted genes in Han--Chinese combining with po1ymerase chainreaction (PCR) and sequencing. We first1y scanned a11 the codingregions of AACT, NACP and ERAB genes in Han--Chinese using a poo1 of200 normal individua1s, 26 poo1s of 10 norma1 individua1s and 33 ADcases. We did not find any SNP in the ERAB and NACP genes but sevenin the AACT gene: G/A (25), A/G(39), C/T(370), T/G(662), C/T (892),T/C(923) and A/G (1332), the first one 1ies both in norma1 popu1ationand AD cases, the second one 1ies on1y in AD cases and the othersfound on1y in norma1 popu1ation. Therefore, we focused on the signalpeptide of the AACT gene, which.contains the first two SNPs, G/A (25),A/G(39), and conducted another scanning of 314 random normalindividua1s and 246 contro1s that matched those AD cases in age,gender and ethnic group. We found that the A/G (39) SNP associatewith AD both in genotype (p<0. 05) and a11e1e frequencies (p<0. 05),whi1e G/A (25) does on1y in genotype (p<0. 05) but not in al1e1efrequencies (p>0. 80). This resu1t is meaningfu1 in both the etiologyand the potentia1 applications of gene diagnose for A1zheimer'sd i sease.