Rs7946

Orientation

plus

is a	snp
is	mentioned by
dbSNP	rs7946
PheGenI	rs7946
nextbio	rs7946
hapmap	rs7946
1000 genomes	rs7946
hgdp	rs7946
ensembl	rs7946
gopubmed	rs7946
geneview	rs7946
scholar	rs7946
google	rs7946
pharmgkb	rs7946
gwascentral	rs7946
openSNP	rs7946
23andMe	rs7946
23andMe all	rs7946
SNP Nexus
SNPshot	rs7946
SNPdbe	rs7946
MSV3d	rs7946

Gene

PEMT

Chromosome

17

Orientation

plus

GMAF

0.4611

Position

17409560

Reference

GRCh37 37.1/131

Max Magnitude

Make rs7946(C;C)

Make rs7946(C;T)

Make rs7946(T;T)

?	(C;C) (C;T) (T;T)	28

rs7946, a SNP in the phosphatidylethanolamine N-methyltransferase PEMT gene and also known as +5465G-A, leads to a V175M (valine to methionine at amino acid position 175) substitution in the PEMT protein, and is a loss of function mutation. Caucasians with nonalcoholic fatty liver are more likely to carry the rs7946 (A), with the effect being most pronounced for rs7946(A;A) genotypes. [PMID 16051693]

However, rs7946(A) carriers are not more likely to have fatty liver, based on a study of many more patients, including ones of Hispanic and African-American descent. [PMID 17012264]

How can this be? One explanation [doi: 10.1096/fj.06-1005ufm] concludes the following:

• Caucasians have a different distribution of this SNP than do Hispanics and African Americans;
• Having this SNP may be necessary, but is not sufficient, to cause fatty liver, as many individuals with the SNP have normal liver fat;
• Probably this SNP does slow the export of fat from liver, but only rs7946 carrying individuals who also take in too many calories too quickly (i.e. overeat) will wind up with fatty livers.

Venter snp
Source	plos
Gene	PEMT
allele	T
frequency	0.733
sift	TOLERATED
HuRef	1103645292864
Disease Association	Deletion of PEMT may be related to liver cancer.

[PMID 21881829] PEMT G523A (V175M) Is Associated with Sporadic Alzheimer's Disease in a Chinese Population

[PMID 16816108] Common genetic polymorphisms affect the human requirement for the nutrient choline.

[PMID 17613168] Gene response elements, genetic polymorphisms and epigenetics influence the human dietary requirement for choline.

[PMID 18230680] Choline metabolism and risk of breast cancer in a population-based study.

[PMID 18789905] Genetic polymorphisms in methyl-group metabolism and epigenetics: lessons from humans and mouse models.

[PMID 19167960] Genetic variants in phosphatidylethanolamine N-methyltransferase and methylenetetrahydrofolate dehydrogenase influence biomarkers of choline metabolism when folate intake is restricted.

GET Evidence
PEMT-V212M
aa_change	Val212Met
aa_change_short	V212M
impact	not reviewed
qualified_impact	Insufficiently evaluated not reviewed
overall_frequency	0.609711
summary