Rs7946

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.

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.

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.

Common genetic polymorphisms affect the human requirement for the nutrient choline.

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

Choline metabolism and risk of breast cancer in a population-based study.

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

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