ABSTRACT
BACKGROUND: Apolipoprotein E (APOE), which its ε4 allele has been reported as a risk factor in late onset Alzheimer's disease (AD), is the main cholesterol carrier in the brain. ATP-binding cassette transporter A1 (ABCA1) gene on chromosome 9, which has been known by genome-wide AD linkage study, has an important role in cellular cholesterol efflux. This study determines the association between sporadic AD and the human ABCA1 and APOE gene polymorphisms in Iranian population. METHODS: 154 AD cases and 162 control subjects from Iranian population were genotyped for APOE genotypes and ABCA1 polymorphism (R219K). RESULTS: The frequency of ε2ε3 genotype was higher in control subjects comparing AD patients but was not significant (13% versus 5.8%) and ε3ε4 genotype frequency was significantly higher in AD cases comparing with control subjects. APOE-ε2 allele frequency in cases was lower than control subjects but this difference was not significant (4.5% versus 8%). Individuals carrying ε4 allele, developed AD 6.5 times more than non-carriers (OR=6.52, 95%CI=2.63-16.17). There was no significant association between ABCA1 polymorphism and AD. CONCLUSION: Unlike other studies, R219K polymorphism was not dependent on gender and APOE-ε4 allele and there was no association between APOE and ABCA1 in AD patients compared to controls.
ABSTRACT
BACKGROUND: Alzheimer's disease as a neurodegenerative disorder is the commonest type of dementia. A growing number of genes have been reported as the risk factors, which increase the susceptibility to Alzheimer's disease. Apolipoprotein E (APOE), which its ε4 allele has been reported as a risk factor in late onset Alzheimer's disease (AD), is the main cholesterol carrier in the brain. The main goal of this study was to assess the role of APOE genotypes and alleles in AD in Iranian population. METHODS: This study was performed in Tehran, Iran from 2007 to 2008. Totally, 154 AD cases and 162 control subjects from Iranian population were genotyped for APOE using PCR method. Genotype and alleles frequencies for APOE were calculated and compared between AD case and control subjects by χ2 or Fisher's exact test. Type one error assumed less than 0.05. RESULTS: The frequency of ε2ε3 genotype was significantly higher in control subjects than AD patients was (13.5% versus 5.2%, P< 0.05) and ε3ε4 genotype frequency was significantly higher in AD cases compared with control subjects. APOE -ε2 allele frequency in cases was lower than that of control subjects but this difference was not significant (4.2% versus 7.7%). CONCLUSION: It seems that individuals carrying ε4 allele, develop AD 6.5 times more than non-carriers do (OR= 6.566, 95% CI= 2.89-14.92). It has been reported that ε4 allele acts in dose- age-dependent manner but we have shown that the risk of developing AD in male APOE -ε4 allele carriers is higher than that of female ε4 carriers.
ABSTRACT
Aberrant expression of the caveolin-1 (CAV1) gene is associated with Alzheimer's disease (AD) brain. We have recently reported a polymorphic purine stretch located at between 1.8 and 1.5 kb flanking the CAV1 gene, whose alleles and genotypes are associated with late-onset AD. Extra-short homozygote haplotypes were observed that were present only in the AD cases. Following an independent case/control study, we report alleles at the other extreme of the allele range, haplotypes of which were observed to be homozygous across the region in the AD cases. We propose that there is a window for the length of motifs and haplotypes in the controls. Homozygosity for shorter and longer motifs and haplotypes was linked with AD in our study. Our findings elucidate novel predisposing haplotypes at the CAV1 gene purine complex, and confirm the role of this region in the etiopathophysiology of late-onset AD.
