Relationship of choline intake with biomarkers of liver health by genotype - a cross-sectional analysis

Document Type

Journal Article

Publication Date

4-28-2025

Journal

The Journal of nutrition

DOI

10.1016/j.tjnut.2025.04.020

Keywords

biomarkers; choline; genetic variation; genotype; liver

Abstract

BACKGROUND: Controlled feeding studies demonstrate that genetic variation in the folate-mediated one-carbon and choline metabolism pathway influence risk of organ dysfunction from consuming choline-deficient (<50mg/day) diets. Whether genotype influences the relationship between choline intake and biomarkers of liver function in the general population remains unknown. OBJECTIVE: Conduct an exploratory cross-sectional analysis to examine the relationship between dietary choline intake with circulating biomarkers of liver function that are commonly impaired by inadequate choline, stratified by genotype across common single nucleotide polymorphisms (SNPs) in one-carbon and choline metabolism related enzymes. METHODS: U.S. adults (≥20y) in the 1999-2002 NHANES who were non-pregnant, non-lactating, had reliable 24-hour dietary recall(s), and blood collected for DNA purification (i.e., complete genetic data) were included (N=1,438). Mean dietary choline intake was estimated using the USDA's Food and Nutrient Database for Dietary Studies and the Choline Content of Common Foods Database. Associations between choline intake and available biomarkers of liver function, adjusted for age (y), BMI, fasting plasma glucose, and total protein and energy intake, were investigated for each SNP, using multiple linear regression. Statistical significance was set at a Bonferroni-corrected p<0.0167 to account for multiplicity across tertiles of choline intake, based on the number of examined genotypes. RESULTS: The lowest tertile of choline intake was not associated with elevated markers of liver dysfunction relative to higher intakes in the entire population or in analyses stratified by common SNPs in one-carbon and choline metabolism pathway enzymes. Higher choline intake was associated with an increase in circulating triglycerides among individuals with the MTR GG (rs1805087) minor genotype. CONCLUSION: In this exploratory NHANES analysis, self-reported choline intakes were not associated with worsening circulating liver function biomarkers in the study population as a whole or when stratified by genotype . Our findings did not recapitulate observed relationships in controlled feeding trials, potentially due to higher habitual choline intakes or limitations of using national surveillance samples to assess diet-x-gene interactions. Further exploration of this research question in prospective cohorts or controlled trials with a broader array of nutritional status markers is warranted.

Department

Clinical Research and Leadership

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