|(A;A)||2.3||Increased chance of Prion Disease (PrP 129 Met homozygote)|
|(A;G)||2.1||Resistance to vCJD (PrP 129 Met/Val heterozygote), 4.6x reduced risk of sporadic CJD and 0.87x reduced risk for late-onset Alzheimer in a Caucasian population|
|(G;G)||2||Resistance to vCJD (PrP 129 Val homozygous), 1.7x reduced risk of sporadic CJD and 0.87x reduced risk for late-onset Alzheimer in a Caucasian population|
The 23andMe blog has a good article about the infectious Creutzfeldt-Jakob disease (vCJD), both people with one or two V are not susceptible to vCJD, the infectious form of CJD.
Historically, since 1991 this SNP has been associated with risk for sporadic Creutzfeldt-Jakob disease, with homozygotes of both types apparently at increased risk compared to heterozygotes.[PMID 1677164]
[PMID 18423780] A further study of 12 individuals of each of the 3 possible genotypes showed that at both 30 minutes and 24 hour time lags, correlations between retrieval-related brain activity and retrieval success were negative for (G;) homozygotes (the more activity, the worse retrieval success), while correlations showed no significance or were positive for (A) homozygotes and heterozygotes. These findings suggest that the rs1799990 SNP affects neural plasticity following learning at a time-scale of minutes to hours.
[PMID 16315279] rs1799990(A;G) heterozygotes were significantly overrepresented (age-adjusted odds ratio, 8.47) in 39 individuals with primary progressive aphasia (PPA), a rare condition of unknown cause, compared to 400+ controls.
|Disease Association||Defects in PRNP are the cause of prion disease with protracted course (MIM:606688); an autosomal dominant presenile dementia with a rapidly progressive and protracted clinical course. The dementia was characterized clinically by frontotemporal features, including early personality changes. Some patients had memory loss, several showed aggressiveness, hyperorality and verbal stereotypy, others had parkinsonian symptoms.|
|Title||Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study|
|Odds Ratio||NR NR|
[PMID 22210626] Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP
|Disease||Prion disease Alzheimer disease Aphasia Jakob-Creutzfeldt disease Fatal familial insomnia Genetic prion diseases not specified|
|CLNDBN||Prion disease, susceptibility to Alzheimer disease, early-onset, susceptibility to Aphasia, primary progressive, susceptibility to Jakob-Creutzfeldt disease Fatal familial insomnia Genetic prion diseases not specified|
|CLNSRC||OMIM Allelic Variant UniProtKB (protein)|
|CLNACC||RCV000014331.7, RCV000014332.7, RCV000014333.7, RCV000014336.24, RCV000014337.24, RCV000020244.2, RCV000118064.2,|
[PMID 16023289] Genetic influences on oxidative stress and their association with normal cognitive ageing.
[PMID 17202849] No association of prion protein gene polymorphisms with Alzheimer's disease in Korean population.
[PMID 18813964] Alzheimer's disease risk variants show association with cerebrospinal fluid amyloid beta.
[PMID 18830724] Assessment of Alzheimer's disease case-control associations using family-based methods.
[PMID 19474294] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
[PMID 20574532] Intermediate phenotypes identify divergent pathways to Alzheimer's disease.
[PMID 1675319] Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease.
[PMID 1682813] CJD discrepancy.
[PMID 7845623] Neuropathological phenotype and 'prion protein' genotype correlation in sporadic Creutzfeldt-Jakob disease.
[PMID 9643750] Genotype at codon 129 and susceptibility to Creutzfeldt-Jakob disease.
[PMID 12867116] Distribution of codon 129 genotype in human growth hormone-treated CJD patients in France and the UK.
[PMID 14970845] Polymorphisms in the prion protein gene and in the doppel gene increase susceptibility for Creutzfeldt-Jakob disease.
[PMID 17047093] Significant association of a M129V independent polymorphism in the 5' UTR of the PRNP gene with sporadic Creutzfeldt-Jakob disease in a large German case-control study.
|qualified_impact||Low clinical importance, protective|
|summary||This variant is associated with some protective effects for prion disease -- individuals homozygous for this variant are less susceptible to Creutzfeldt-Jakob, and Papua New Guinea individuals heterozygotes at this site are less susceptible to kuru.|
[PMID 23399523] The association between the methionine/valine (M/V) polymorphism (rs1799990) in the PRNP gene and the risk of Alzheimer disease: an update by meta-analysis.