rs669

A SNP in the KLRG1 gene on chromosome 12. Its most notable genotype is C;C: 3.8x or higher increased risk for Alzheimers

Gene
KLRG1
Location
Chr 129,079,672 (GRCh38)
Highest magnitude
2.0Worth knowing
Tested on
23andMe, AncestryDNA, FamilyTreeDNA
Minor allele frequency
26%

Genotypes

Plus strand, as in 23andMe and AncestryDNA files.

  1. T;TGoodnormalTypical · 0.059% of people
  2. C;TNot ratedpossibly increased risk for AlzheimersTypical · 0.034% of people
  3. C;CMost notableBad3.8x or higher increased risk for AlzheimersWorth knowing · 2.07% of people

SNPedia records rs669 on the minus strand: (A;A), (A;G), (G;G). Magnitude rates how notable a genotype is from 0 to 10, not how risky it is.

Frequency

Share of each genotype in 11 HapMap populations.

  • AverageT;T 59% C;T 34% C;C 7%
  • European ancestry (Utah)T;T 46% C;T 45% C;C 9%
  • Han Chinese (Beijing)T;T 82% C;T 17% C;C 2%
  • Japanese (Tokyo)T;T 91% C;T 8% C;C <1%
  • Yoruba (Nigeria)T;T 44% C;T 44% C;C 12%
  • African ancestry (Southwest US)T;T 46% C;T 47% C;C 7%
  • Chinese (Denver)T;T 86% C;T 13% C;C <1%
  • Gujarati IndianT;T 66% C;T 31% C;C 3%
  • Luhya (Kenya)T;T 56% C;T 36% C;C 8%
  • Mexican ancestry (Los Angeles)T;T 35% C;T 52% C;C 14%
  • Maasai (Kenya)T;T 45% C;T 45% C;C 10%
  • TuscanT;T 50% C;T 42% C;C 8%

Conditions, medicines and genes

Notes

From SNPedia

Show notes, about 200 words

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. 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.. 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.

Source and license

Adapted from rs669 on SNPedia, using a snapshot taken October 16, 2026. SNPedia content is shared under CC BY-NC-SA 3.0 US, and this page is shared under the same license.

SNPedia is a community-edited wiki. Its entries can be incomplete, out of date or wrong, and nothing here is a diagnosis or medical advice. Magnitude is a community rating of how interesting a genotype is, not a risk score.