Relationship Between PEMT Gene rs7946 Polymorphism and Nutritional Choline Status in Association With Nonalcoholic Fatty Liver Risk

OBJECTIVES: Phosphatidylethanolamine N-methyltransferase (PEMT) rs7946 genetic polymorphism and nutritional choline status on nonalcoholic fatty liver (NAFL) risk have not been well elucidated. The aims of the study were to investigate the choline-polymorphic relationship on NAFL risk. METHODS: The study recruited 253 patients with metabolic disorders from one regional hospital in 2020. By abdominal ultrasound diagnosis, 99 patients with hepatic steatosis (HS) and 99 age- and sex-matched controls without HS were included for the study. Habitual dietary choline intakes were assessed using validated quantitative FFQ by a face-to-face interview. PEMT rs7946 (V175M, G to A substitution) polymorphism, blood choline concentrations and metabolic disorders factors were analyzed for their interaction with HS risk. RESULTS: Genetic distribution of PEMT rs7946 polymorphism significantly differed in controls (GG: 48%, GA, 32%, AA, 20%) and in the HS cases (GG: 69%, GA: 26%, AA: 5%) (p = 0.003). Higher values of body mass index (BMI), serum triglycerides (TG), insulin resistance (HOMO-IR), alanine aminotransferase and lower levels of HDL were associated with HS cases. Plasma free choline levels were significantly higher in HS cases (median:12.4 μM, quartile range (9.9–14.8)) than in controls (median: 10.6 μM, quartile range (9.3–12.8)) (p = 0.001). The daily dietary intake of total choline and the choline derivatives did not differ between the two groups. After adjustment of age, gender, BMI, energy consumption, fiber intake, and blood metabolic markers (TG, LDL, HDL and HOMA-IR), odds ratios of HS were 7-fold increase (OR: 7.6, 95% CI: 2.3–24.4) for patients with PEMT rs7946 GG genotype of high plasma choline level (> median levels: 11.6 μM) as compared with GA/AA genotype of plasma choline level lower than 11.6 μM. CONCLUSIONS: The PEMT rs7946 GG genotype in combination with high plasma choline levels was associated with increased risks of hepatic fat accumulation in patients with metabolic disorders. FUNDING SOURCES: The Ministry of Health and Welfare-affiliated Taipei Hospital. The Ministration of Science and Technology, Taiwan, ROC.