Nutrigenetic Impact of PEMT Gene Polymorphism Rs7946 On Choline Metabolism and Its Role in Personalised Nutrition

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.

PEMT gene, rs7946, polymorphism, SNP, phosphatidylcholine choline, nutrigenetics, NAFLD, one carbon metabolism.

1. Wu, Z., Song, S., He, Y., Wang, Q., & Yang, H. (2023). Phosphatidylethanolamine N-methyltransferase gene polymorphism rs7946 is associated with NAFLD risk: A meta-analysis. Genes & Nutrition, 18(1), 15. [Google Scholar] [Crossref]

2. Zhu, X., Song, X., Zhou, X., & Zhang, L. (2020). Influence of PEMT gene variants on cardiometabolic risk factors: a cross-sectional study. Lipids in Health and Disease, 19(1), 213. [Google Scholar] [Crossref]

3. Tan, H., Ueland, P., Vollset, S., & Choline, M. (2016). Sex-specific effects of PEMT polymorphism on choline metabolism and homocysteine concentrations. American Journal of Clinical Nutrition, 104(6), 1636–1642. [Google Scholar] [Crossref]

4. Harrison, C., Jones, P., & Zeisel, S. (2020). Estrogen regulation of PEMT and implications for choline requirements in women. Nutrients, 12(9), 2751. [Google Scholar] [Crossref]

5. Myoidzk D, et al. (2021). Associations between choline metabolism and anxiety-related behavior: Insights from genetic profiling. Psychiatr Genet, 31(4), 152–159. [Google Scholar] [Crossref]

6. Myoidzk, L., Krzyzanowska, M., &Polanska, K. (2021). Choline intake and anxiety symptoms in adults with PEMT variants. Nutritional Neuroscience, 24(2), 134–143. [Google Scholar] [Crossref]

7. He, Y., Zhang, R., & Chen, J. (2024). Impact of PEMT rs7946 on choline-related cognitive performance: A population-based cohort study. Neurobiology of Aging, 130, 42–49. [Google Scholar] [Crossref]

8. Zhang, W., Cheng, J., & Li, F. (2024). Genetic polymorphisms in choline metabolism pathways and colorectal cancer risk: A case-control study. Frontiers in Oncology, 14, 1279856. [Google Scholar] [Crossref]

9. Ganz, A., Cohen, L., Swersky, C., Stabler, S., Allen, R., & Zeisel, S. (2017). Genetic variation in choline-metabolizing enzymes alters choline metabolism in young women consuming choline intakes meeting current recommendations. The Journal of Nutrition, 147(4), 621–631. [Google Scholar] [Crossref]

10. Sharma, A., Choudhury, S., &Sahoo, S. (2019). Homocysteine levels and PEMT genotype interactions in Indian adults. Indian Heart Journal, 71(3), 234–239. [Google Scholar] [Crossref]

11. Da Costa &Resseguie, M. E, (2017). Estrogen induces PEMT gene expression in primary hepatocytes. FASEB Journal, 21, 2622–2632 [Google Scholar] [Crossref]

12. Li, N., Wu, S., & Sun, C. (2022). Phosphatidylethanolamine N methyltransferase: from Functions to Diseases. Aging and Disease, 13(6), 1560–1575. https://doi.org/10.14336/AD.2022.102 [Google Scholar] [Crossref]

13. Loinard González, A. A. P., Malysheva, O. V., Klatt, K. C., & Caudill, M. A. (2022). Genetic Variants in One Carbon Metabolism and Their Effects on DHA Biomarkers in Pregnant Women: A Post Hoc Analysis. Nutrients, 14(18):3801. https://doi.org/10.3390/nu14183801 [Google Scholar] [Crossref]

14. Niculescu, M. D., & Zeisel, S. H. (2022). Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. The Journal of Nutrition, 132(8Suppl), 2333S–2335S. [Google Scholar] [Crossref]

15. Piras, I. S., Raju, A., Don, J., Schork, N. J., Gerhard, G. S., &DiStefano, J. K. (2022). Hepatic PEMT expression decreases with increasing NAFLD severity. International Journal of Molecular Sciences, 23(16), 9296. https://doi.org/10.3390/ijms23169296. [Google Scholar] [Crossref]

• Most Advanced Construction Material for Typical Boilers
• Evaluating the Influence Factors of Media on Investor Sentiment Towards Stock Market Investments.
• To Compare the Effectiveness of Manual Traction and Mechanical Traction in Patient with Cervicogenic Headache
• Is Green Human Resource Management the Newest Trend or A Strategic Necessity?
• Battery Hazards and Safety: A Comprehensive Review for Lithium -Ion Battery System