rs2254958

While the ApoE4 allele (rs429358(C)) is widely accepted as the predominant genetic risk factor for Alzheimer's disease, there are likely to be numerous other factors, both genetic and environmental, associated to lesser degrees with susceptibility to the disease. Genes influencing the immune system, and in particular susceptibility to viral infections such as herpes, may be among such factors. This SNP, located in the promoter region of the EIF2AK2 gene and thus implicated in the activation of HIV and HSV-1 viruses, is seen more commonly in ~300 Alzheimer patients than in the same number of controls. The risk allele is rs2254958(C). The odds ratio is reported to be 1.61 (CI: 1.02-2.55) for rs2254958(C;C) homozygotes, and 1.24 (CI: 0.80-1.93) for rs2254958(C;T) heterozygotes, compared with rs2254958(T;T) homozygotes. NOTE: the study cited above is now over a decade old, was based on a relatively small number of patients, and to our knowledge it has not been replicated. Furthermore, the frequency of the rs2254958(C) allele is quite high in (though also highly variable between) different populations, and only one ethnicity was studied in the 2008 publication. Overall, a decade+ after publication, it seems reasonable to question the significance of the conclusions reached by the 2008 study cited above.