rs1799990

rs1799990, also known as Met129Val or M129V, is a SNP in the prion protein PRNP gene. The more common rs1799990(A) allele encodes the Met (methionine). 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. More recently, this SNP has been related to long-term memory with (A;A) and (A;G) individuals recalling 17% more words than (G;G) individuals at 24h following learning. 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. 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.

A;A

This genotype encodes for a homozygous Methionine at position 129 of PRNP, the Prion Protein gene (PrP-129MM). Unlike the protective M/V heterozgotes and V homozygous, homozygosity at this residue is associated with an increased susceptibility to sporadic CJD and and confers susceptibility against vCJD. All reported cases of vCJD, (linked to ingestion of 'mad cow disease' contaminated meat) have been 129 Met homozygous

A;G

This genotype codes for Met/Val heterozygote at codon 129 in PrP, the Prion Protein. This is strongly protective against development of sporadic, and confers resistance against vCJD. Studies in Papua New Guinea showed that this genotype prevents transmission of kuru , a form of Prion disease transmitted by cannibalism. So eat as many brains as you want! A total of 4228 cases and 4324 controls in 16 case-control studies were included in the meta-analysis. The results indicated that the variant V allele carriers (VV+MV) had a 13% decreased risk of AD, when compared with the homozygote MM A 2006 study compared 593 Germans with sporadic CJD (sCJD) to 748 healthy controls. The researchers found an unusual pattern - people with one copy of each variant at rs1799990, a SNP in the gene PRNP, were less likely to have sCJD compared to those who had two identical copies of either the A or G type. People with the AG genotype had 4.6 times lower odds of sCJD compared to those with AA; a G at both copies of the SNP reduced a subject's odds of having sCJD 1.7 times.PMID 17047093 All reported cases of vCJD, (linked to ingestion of 'mad cow disease' contaminated meat) have been 129 Met homozygous PMID 22505363

G;G

This genotype codes for Val/Val homozygous at codon 129 in PrP, the Prion Protein. This is slightly protective against development of sporadic CJD, and confers resistance against vCJD. Studies in Papua New Guinea showed that this genotype prevents transmission of kuru PMID 19923577, a form of Prion disease transmitted by cannibalism. So eat as many brains as you want! A total of 4228 cases and 4324 controls in 16 case-control studies were included in the meta-analysis. The results indicated that the variant V allele carriers (VV+MV) had a 13% decreased risk of AD, when compared with the homozygote MM A 2006 study compared 593 Germans with sporadic CJD (sCJD) to 748 healthy controls. The researchers found an unusual pattern - people with one copy of each variant at rs1799990, a SNP in the gene PRNP, were less likely to have sCJD compared to those who had two identical copies of either the A or G type. People with the AG genotype had 4.6 times lower odds of sCJD compared to those with AA; a G at both copies of the SNP reduced a subject's odds of having sCJD 1.7 times.PMID 17047093 All reported cases of vCJD, (linked to ingestion of 'mad cow disease' contaminated meat) have been 129 Met homozygous PMID 22505363