|(A;G)||possibly increased risk for Alzheimers|
|(G;G)||2||3.8x or higher increased risk for Alzheimers|
rs669 is a SNP in the alpha-2-macroglobulin A2M gene. In dbSNP orientation, the rs669(A) allele encodes an isoleucine, and the rs669(G) allele encodes a valine; the SNP is also known as the Ile/Val variant.
On its own, rs669 was not seen to reproducibly and independently increase risk for Alzheimer's disease in several studies of ~200 Italian patients. However, the T-C-A haplotype of rs12316150-rs1050283-rs669 was associated with both early- and late-onset Alzheimer's disease. The majority of the disease risk from this haplotype was based on rs1050283.[PMID 18191876]
The original 2004 study of 148 Italian sporadic AD patients yielded an odds ratio for the rs669(G;G) genotype (as oriented in dbSNP orientation) of 3.81 (CI: 1.66-8.75). The presence of rs2333227(C;C), in addition to rs669(G;G), appears to synergistically increase the risk of AD to an odds ratio of 25.5 (CI: 4.65-139.75), regardless of ApoE status.[PMID 15023809]. However, the more recent 2014 meta-analysis suggests that there is not 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.
[PMID 21122033] Leukoaraiosis is associated with genes regulating blood-brain barrier homeostasis in ischaemic stroke patients
|Disease||ALPHA-2-MACROGLOBULIN POLYMORPHISM Alzheimer disease|
|CLNDBN||ALPHA-2-MACROGLOBULIN POLYMORPHISM Alzheimer disease, susceptibility to|
|CLNSRC||OMIM Allelic Variant UniProtKB (protein)|
[PMID 23186781] Association of polymorphisms in the LRP1 and A2M genes with Alzheimer's disease in the Northern Chinese Han population
[PMID 23238918] Genome-wide pathway analysis of a genome-wide association study on multiple sclerosis.
[PMID 24756728] Influence of Alpha-2-Macroglobulin 5 bp I/D and Ile1000Val Polymorphisms on the Susceptibility of Alzheimer's disease: A Systematic Review and Meta-analysis of 52 Studies