Rs199768005

The minor allele of rs199768005 (A)(p.V236E, T/C sic) is a rare mutation (0.12%) in the APOE gene. It is one of only two protein APOE variants with MAF>0.1% in the Exome Variant Server (EVS, http://evs.gs.washington.edu/EVS/),

A study found that carriers of this rare mutation had a markedly reduced risk for AD (OR=0.10, 0.03-0.45). Only 2 of 25 heterozygotes had AD versus 23 controls (4128 LOAD, and 4986 controls). The minor allele of rs199768005 is in phase with the APOE epsilon 3 allele. p.V236E divides the epsilon 3 haplotype into epsilon 3b (the minor allele of rs199768005) and epsilon 3a (major allele of rs199768005). The risk of AD among those with epsilon 3b genotype was substantially reduced(OR=0.11,0.02-0.36, P=2.32x10-3). This decrease in AD risk was AD independent of the epsilon 2, 3 and 4 alleles. If confirmed, this rare genotype might reduce risk of AD more than the well-known epsilon 2 genotype.

Within the context of AD, the minor allele of rs199768005 appears to reduce disease risk. However, it is cited on this page and dbsnp as pathogenic in the context of Familial type 3 hyperlipoproteinemia.