Association Of Family History And Polymorphism In ACT-51G/T, IL-1α-889C/T, LRP766C/T And NOS-Ⅲ298G/T With Alzheimer's Disease In Chinese Han Population

Background: Alzheimer's disease (AD) is perhaps the most devastating of all degenerative disorders in the elderly. Although the cause of AD is not established, a genetic basis is strongly suspected. It is well established that early-onset familial cases of AD are attributable to mutations on APP gene on chromosome 21 or to the presenilin 1gene on chromosome 14, or presenilin 2 on chromosome 1. For late-onset AD, the association with the ApoE ε 4 allele on chromosome 19 is consistently identified both in familial and also sporadic individual cases. In spite of the important impact of polymorphisms in these genes in AD, it is estimated to only account for a small part of AD cases. This suggests that other genetic loci for AD remain to be discovered. Recently, linkage studies have reported some new susceptible gene associated with AD. But these results are conflicted in different areas or rates, more and more cases are needed to define these associations.Objective: To identify the genotypes and alleles frequencies of susceptible genes in the Chinese Han population (molecular epidemiology), verify and explore epidemiological and genetic pattern of AD in the Chinese elderly and to develop approaches for early diagnosis, further understanding pathogenic mechanism of AD.Methods: Our samples were recruited from the outpatient clinics and population-based epidemiological survey. The diagnosis of AD met with the criteria of NINCDS/ ADRDA about probable AD, and the degree of severity was according to GDS. The real time PCR method was used to detect the polymorphisms of ACT-51G/T, IL-1α -889C/T, LRP 766C/T 和 NOS-Ⅲ 298 G/T, and PCR-RFLP was used to determine ApoE polymorphism. All AD patients conducted cranial CT or MRI. Multiple logistic regression and chi square test were performed to explore the risk factor for AD.Results: (1) The frequency of G/G, G/T and T/T genotype of ACT were 12.50%,42.83% and 44.67% respectively among AD patients, and 12.57% , 52.24% and 35.19% respectively among non-dementia controls. The individuals with T/T genotype and T allele had increased risk for AD (OR for T/T vs. G/G: 1.55, 95%CI: 1.20~2.00, P=0.003). Adjusted for age and sex, the risk of T/T and G/T genotypes for AD was still detected. In multivariate analysis, T/T and G/T genotypes and T allele of IL-1α-889, age≥65 years and...