Our findings do not support the fact that the previously reported positive association between A2M deletion polymorphism and AD modifies the disease risk in the studied population.Am.J. Med.Genet.(Neuropsychiatr.Genet.)96:775-777, 2000.
These results indicated that A2M-D allele was probably a weak AD protective factor, and there was a possible interaction of APOE-epsilon 4 and A2M-G alleles to increase AD risk in Mainland Han Chinese.
Our results failed to demonstrate an association between this polymorphism and Japanese sporadic AD, and the A2MI1000V mutation does not seem to be a risk factor per se for sporadic AD.
In conclusion, our data suggests that the A2M D allele is a modest risk factor for late-onset sporadic AD in Koreans, and the AD risk conferred by the A2M D allele increases in APOE epsilon4 negative subjects.
The coexistence of at least one allele Val (A2M-Val+) and one allele C (LRP1-C+) increased up two times the risk of AD (OR 2.32; 95% CI 1.23-4.35; p<0.009).
Earlier identified regions on chromosomes 10 and 12, nor the effect of the alpha-2-macroglobulin (A2M) I/D polymorphism on Alzheimer's disease could be confirmed in our study.
Therefore, we conclude that in our samples, the A2M I/V genotype might be a susceptibility variant, even with minor effect, for both sporadic AD and PD.
Substantial linkage disequilibrium was detected across the gene as a whole, and haplotype analysis also showed significant association between AD and groups of A2M polymorphisms.
There was no significant difference in the severity of CAA between individuals with the A2M deletion allele and those without in the AD, non-AD, or total cases.
The meta-analysis suggests that there is no enough evidence for associations of A2M gene polymorphisms (5 bp I/D, Ile1000Val) with AD risk at present, even after stratification by ethnicity and APOE ε4 with genotypes of polymorphism sites.
Through combination-analysis of the data about the A2M-I/D and the A2M-Ile1000Val variants, the A2M gene was suggested to be associated with Alzheimer's disease.
Drug response from pharmacogenetic viewpoint after 3-year follow-up of AD patients and Clinical Dementia Rating (CDR) analysis demonstrated that AD patients carrying bigenic genotype IL-6 CC-A2M AG (ΔCDR = 4.5) and male patients with IL-6 CC genotype (ΔCDR = 3.83) provided the best response and the A2M GG genotype (ΔCDR = 7.97) and bigenic genotype IL-6 GG-A2M GG (ΔCDR = 8.5) conferred the worst response to the rivastigmine, suggesting likely involvement of genotype-specific response to rivastigmine therapy in AD patients.
Recent reports have suggested that genetic polymorphisms in the alpha-2 macroglobulin (A2M) gene are associated with an increased risk for Alzheimer's disease.
To evaluate the genetic factors for AD among a Chinese population in Taiwan, we studied the polymorphisms of six candidate genes of Alzheimer's disease (AD), including the regulatory region of apolipoprotein E (Apo-E, G-186T), the promoter of apolipoprotein E (Apo-E, A-491T), the bleomycin hydrolase gene (BH, A1450G), a mutation of alpha(2)-macroglobulin gene (A2M G2998A), low-density lipoprotein receptor-related protein gene (LRP, C766T), and alpha(1)-antichymotrypsin gene (ACT, -15Ala/Thr) in AD patients and non-affected elder individuals among Taiwanese Chinese.
Two other genes with mixed support as genetic risk factors for AD, A2M (alpha-2-macroglobulin) and LRP (low-density lipoprotein receptor-related protein), have not been studied in relation to memory among nondemented adults.