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.
|Disease Association||Deletion of PEMT may be related to liver cancer.|
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|qualified_impact||Insufficiently evaluated not reviewed|