{{Rsnum
|rsid=669
|Gene=A2M
|Chromosome=12
|position=9079672
|Orientation=minus
|ReferenceAllele=A
|MissenseAllele=G
|GMAF=0.2649
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=A2M
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 46.4 | 44.6 | 8.9
| HCB | 81.6 | 16.9 | 1.5
| JPT | 91.2 | 8.0 | 0.9
| YRI | 43.5 | 44.2 | 12.2
| ASW | 45.6 | 47.4 | 7.0
| CHB | 81.6 | 16.9 | 1.5
| CHD | 86.0 | 13.1 | 0.9
| GIH | 66.3 | 30.7 | 3.0
| LWK | 56.4 | 35.5 | 8.2
| MEX | 34.5 | 51.7 | 13.8
| MKK | 45.2 | 44.5 | 10.3
| TSI | 50.0 | 42.2 | 7.8
| HapMapRevision=28
}}
[[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}}

{{omim
|desc=ALPHA-2-MACROGLOBULIN POLYMORPHISM
|id=103950
|rsnum=669
|variant=0001
}}

{{PMID Auto
|PMID=21122033
|Title=Leukoaraiosis is associated with genes regulating blood-brain barrier homeostasis in ischaemic stroke patients
}}

{{ClinVar
|rsid=669
|Reversed=1
|FwdREF=A
|FwdALT=G
|REF=T
|ALT=C
|RSPOS=9232268
|CHROM=12
|GMAF=0.2656
|dbSNPBuildID=36
|SSR=0
|SAO=1
|VP=0x05036800000015051f110101
|GENEINFO=A2M:2
|GENE_NAME=A2M
|GENE_ID=2
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000012.11:g.9232268T>C
|CLNORIGIN=1
|CLNSIG=255
|Tags=RV;PM;PMC;S3D;SLO;VLD;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;OM
|CAF=0.7351; 0.2649
|CLNACC=RCV000019801.1; RCV000019802.1
|CLNDBN=ALPHA-2-MACROGLOBULIN POLYMORPHISM; Alzheimer disease, susceptibility to
|CLNSRC=OMIM Allelic Variant
|CLNSRCID=103950.0001
|COMMON=1
|Disease=ALPHA-2-MACROGLOBULIN POLYMORPHISM; Alzheimer disease
}}

{{GET Evidence
|gene=A2M
|aa_change=Ile1000Val
|aa_change_short=I1000V
|impact=not reviewed
|qualified_impact=Insufficiently evaluated not reviewed
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs669
|overall_frequency_n=3288
|overall_frequency_d=10294
|overall_frequency=0.319409
|n_genomes=32
|n_genomes_annotated=0
|n_haplomes=42
|n_articles=0
|n_articles_annotated=0
|pph2_score=0.005
|nblosum100=-4
|autoscore=0
|webscore=N
}}

{{PMID Auto
|PMID=23186781
|Title=Association of polymorphisms in the LRP1 and A2M genes with Alzheimer's disease in the Northern Chinese Han population
}}

{{PMID Auto
|PMID=23238918
|Title=Genome-wide pathway analysis of a genome-wide association study on multiple sclerosis.
}}

{{PMID Auto
|PMID=24756728
|Title=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
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | FTDNA}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}