Reference Number: 678
Year: 2025
Link: Link to original paper
Health: Liver disease
Summary
Abstract:
The PEMT (phosphatidylethanolamine N-methyltransferase) gene plays a critical role in the endogenous synthesis of phosphatidylcholine, an essential compound in lipid metabolism and liver health. The single nucleotide polymorphism (SNP) rs7946 (V175M) within the PEMT gene influences the enzymatic activity and structural stability, leading to altered choline metabolism. Individuals carrying Aallele exhibit reduced PEMT activity, predisposing themto non-alcoholic fatty liver disease (NAFLD), elevated homocysteine levels, and reproductive or cognitive risks under low choline diets. This impact is modulated by sex hormones, particularly oestrogen, rendering postmenopausal women more susceptible. This review summarises recent findings linking PEMT rs7946 variants with metabolic, hepatic, and psychological outcomes and explores gene diet interactions that informs genotype based nutritional recommendations. It also suggests tailored choline intake strategies based on genotype. We argue for the integration of PEMT screening in nutritional counselling, especially for vulnerable groups. Future nutrigenetics research is necessary to refine these guidelines and assess long-term impacts.
Summary of Findings
Dr. Shamya Reny’s paper looks at how a common genetic variant in the PEMT gene, called rs7946, affects the way your body handles choline, an essential nutrient needed for liver health, brain function, and lipid (fat) metabolism. The goal of the paper is to show how this genetic difference can change a person’s nutritional needs and why personalised nutrition matters.
The PEMT gene helps the liver make phosphatidylcholine, a key molecule used to build cell membranes and to package and export fats from the liver. Normally, your body can make some phosphatidylcholine on its own, especially when your diet is low in choline. But the rs7946 variant changes how well this process works.
The rs7946 variant is a single?letter DNA change: a G is replaced by an A. This changes one amino acid in the PEMT enzyme, from valine to methionine. According to the paper, this small change makes the enzyme less stable and less efficient. People who carry the A allele (especially if homozygous) tend to have reduced PEMT activity.
This matters because if PEMT works less effectively, the body becomes more dependent on dietary choline. Without enough choline, the liver struggles to make phosphatidylcholine, which can lead to fat building up in the liver. This is why people with the A allele are more likely to develop non alcoholic fatty liver disease (NAFLD) when their choline intake is low. They may also be more vulnerable to elevated homocysteine, which is linked to cardiovascular risk, and to certain reproductive or cognitive problems if choline intake is inadequate.
The paper also highlights the important role of oestrogen. Oestrogen naturally increases PEMT activity, helping the body make more phosphatidylcholine. This means premenopausal women often have a built?in advantage: they can tolerate lower choline intake better than men or postmenopausal women. But if a woman carries the rs7946 A allele, this hormonal protection is weaker. And after menopause, when oestrogen levels fall, women with the A allele become much more vulnerable to choline deficiency and its metabolic consequences.
Dr. Reny argues that this is a perfect example of nutrigenetics the idea that our genes influence how we respond to nutrients. The rs7946 variant shows that a “one size fits all” nutrition guideline doesn’t work for everyone. Some people genuinely need more choline than others to stay healthy. The paper suggests that genetic screening for PEMT variants could help identify individuals at higher risk, especially postmenopausal women, pregnant women, and people with metabolic vulnerabilities.
The review concludes that personalised nutrition should take PEMT genotype into account when giving dietary advice. It also calls for more research to refine choline intake recommendations and to understand long?term health outcomes in people with reduced PEMT activity. Overall, the message is simple: your genes influence how much choline you need, and knowing your PEMT status can help tailor your diet to protect your liver, metabolism, and overall health.
Nikki’s note: This paper refers to the A allele but in the LifecodeGX reports it refers to this as a T. This is perfectly normal and depends on the naming convention of the testing company. Every gene has a forward and a reverse strand so there is always a complimentary partner and the partner for A is T.
Significance for the Baker
For someone who carries the rs7946 variant on the PEMT gene, personalised nutrition focuses on supporting the body’s reduced ability to make phosphatidylcholine, which is essential for healthy fat and cholesterol handling in the liver. This usually means ensuring consistent, adequate choline intake from foods like eggs, soy, legumes, and certain vegetables, because people with the A allele rely more heavily on dietary choline than those with the typical version of the gene. It also helps to maintain good levels of methyl donor nutrients such as folate, B12, and betaine—because they support the same metabolic pathways that PEMT feeds into. Since oestrogen normally boosts PEMT activity, postmenopausal women or anyone with low oestrogen may need to be especially attentive to choline rich foods. Overall, the aim is to give the liver enough raw materials to keep exporting fats efficiently and prevent build?up, tailoring diet to compensate for the gene’s reduced efficiency. Betaine and choline are deeply interconnected; they sit on the same metabolic pathway, and your body can convert one into the other depending on what it needs. Betaine is in beetroots so the beetroot, black pepper and feta batards bread served with eggs (scrabbled / poached), and use any of the diversity blends that contain legumes (peas, beans and lentils). Increasing the betaine in your diet also increases the choline.
