rs7946 — PEMT Val175Met

PEMT — Your Internal Choline Factory

PEMT (phosphatidylethanolamine N-methyltransferase) is an enzyme in the liver that produces phosphatidylcholine ¹¹ A major component of cell membranes and bile, essential for fat transport from the liver (PC) from phosphatidylethanolamine using three sequential methylation reactions. Phosphatidylcholine is a critical component of cell membranes, bile (needed for fat digestion), and VLDL particles (which transport fat from the liver). PEMT is the body's primary internal source of choline, reducing dependence on dietary intake.

The Mechanism

The Val175Met variant ²² Valine-to-methionine substitution at position 175 of the protein (p.Val175Met) (rs7946) substitutes valine with methionine at position 175 of the PEMT protein. The T allele (Met) reduces enzyme activity by approximately 30%, meaning less phosphatidylcholine is produced internally. This shifts the burden to dietary choline sources. Each methylation reaction requires one S-adenosylmethionine (SAM) ³³ SAM is the body's universal methyl donor molecule, so PEMT activity is also dependent on overall methylation capacity. Notably, the T allele is very common in Europeans (75% frequency) but much rarer in East Asians (24%).

The Gender Dimension

PEMT is an estrogen-responsive gene — estrogen upregulates its expression. This means premenopausal women with PEMT variants may be partially protected by their estrogen levels. However, postmenopausal women with PEMT variants face a particularly high risk of choline deficiency because they lose both the genetic capacity and the hormonal support for internal choline production.

The Evidence

A clinical trial at UNC Chapel Hill⁴⁴ A clinical trial at UNC Chapel Hill
da Costa KA et al. FASEB J 2006 — common genetic polymorphisms affect the human requirement for the nutrient choline demonstrated that women with PEMT variants who consumed a low-choline diet developed liver dysfunction (fatty liver, elevated liver enzymes) significantly more often than women without the variant. A Japanese study⁵⁵ Japanese study
Song J et al. PEMT Val175Met and NASH susceptibility, 2007 confirmed that the variant is significantly more frequent in NASH patients. More recent research shows sex-specific effects⁶⁶ sex-specific effects
PEMT rs7946 polymorphism and sex modify choline effect on hepatic steatosis risk, 2023 where adequate dietary choline intake modifies the risk of hepatic steatosis differently in men and women.

Practical Implications

Egg yolks are the most practical dietary source of choline (about 150mg per yolk). Liver is even richer but less commonly consumed. If you carry the T allele, deliberately including choline-rich foods daily is one of the simplest and most impactful dietary strategies informed by your genetics. This is especially important if you also have MTHFD1 variants (rs2236225), which independently increase choline needs.

Interactions

PEMT interacts with MTHFD1 (rs2236225) — both variants increase choline requirements, and the combined effect can be substantial. It also interacts with MTHFR (rs1801133), as PEMT activity depends on SAM from the methylation cycle.