Associations of plasma betaine, plasma choline, choline intake, and MTHFR polymorphism (rs1801133) with anthropometric parameters of healthy adults are sex‐dependent

Abstract

Background Choline and its metabolites apppear to have relationships with body mass index (BMI), body fat, and body weight, but the research results have proved inconsistent. We thus investigated the associations of plasma levels of trimethylamine N‐oxide (TMAO), choline, and betaine with anthropometric measurements, including modulatory effects of genetics and diet. Methods The study was performed on a group of 421 adults, aged 20–40 years, who had been recruited in Poland. Plasma concentrations of choline, betaine, and TMAO were determined using reverse‐phase ultra‐high‐performance liquid chromatography electrospray ionisation mass spectrometry. The following polymorphisms were genotyped using TaqMan probes: rs180113 (MTHFR), rs70991108 (DHFR), rs2236225 (MTHFD1), and rs7946 and rs12325817 (PEMT). We employed multivariate linear regression to examine the associations between anthropometric measurements, one‐carbon metabolism metabolites, and genotypes. Results Higher plasma choline was associated with higher BMI (β = 0.17; p < 0.01), body weight (β = 0.11; p < 0.05), body fat mass (FM) (β = 0.10; p < 0.05), and waist circumference (WC) (β = 0.14; p < 0.01), whereas higher choline intake was associated with lower body FM (β = −0.14; p < 0.01) and lower WC (β = −0.12; p < 0.01). After stratification by sex, plasma betaine was found to be associated with lower BMI (β = −0.20; p < 0.05) and body weight (β = −0.16; p < 0.05) in men only, whereas choline intake was associated with lower body FM (β = −0.19; p < 0.05) and waist‐to‐hip ratio (WHR) (β = −0.19; p < 0.05) and MTHFR CC genotype was associated with WHR (β = 0.15; p < 0.05) in women only. Conclusions Higher plasma betaine and higher dietary choline are associated with lower FM and body weight, whereas higher plasma choline is positively associated with body weight status and adiposity. Moreover, these associations appear to be sex‐specific.

Gene–environment interactions in human health

“…This brief editorial provides just a snapshot of some of the key insights into gene-environment interactions and relationships with health outcomes presented in the 12 original articles that follow. [1][2][3][4][5][6][7][8][9][10][11][12] The results and discussion presented herein highlight the important role of diet (and potentially other environmental factors) with respect to gene expression and ultimately an individual's health status. A better understanding of gene-environment interactions and the biological pathways that underpin these relationships will help identify diet or metabolic targets for interventions aimed at maintaining or improving health throughout the lifecycle.…”

“…7 Another somewhat similar analysis reported associations between dietary and plasma measurements of choline and betaine and better body composition outcomes, as well as a significant association between CC genotype of MTHFR (rs1801133) and waist to hip ratio. 8 Interestingly, these results were also sex-specific with stronger associations among females compared to males, 8 highlighting further complexity when analysing, interpreting and understanding gene-environment interactions.…”

“…This special issue of the Journal of Human Nutrition and Dietetics comprises a compilation of 12 original research articles that focus on associations between genes and environment as well as gene-environment interactions in human health, with a particular emphasis on diet, body composition and metabolic health. [1][2][3][4][5][6][7][8][9][10][11][12] Human gene-environment associations and interactions can be investigated using a range of study designs, including the classic twin study, which collects data from monozygotic and dizygotic twin pairs and typically uses some form of structural equation modelling to estimate the proportion of variation in a trait explained by genes, shared environment and unique environment. 13 Other study designs include the traditional candidate-gene study, which examines associations between genes and environmental exposures, usually where there is a known link between the gene and the exposure, or the more complex genome-wide association study, which usually assumes no prior hypothesis and examines the entire genome for interactions with various environmental exposures.…”

“…This brief editorial provides just a snapshot of some of the key insights into gene–environment interactions and relationships with health outcomes presented in the 12 original articles that follow 1–12 . The results and discussion presented herein highlight the important role of diet (and potentially other environmental factors) with respect to gene expression and ultimately an individual's health status.…”

“…Diet is one of the key aspects of the environment that impacts health along with others such as lifestyle, physical activity and the gut microbiome. This special issue of the Journal of Human Nutrition and Dietetics comprises a compilation of 12 original research articles that focus on associations between genes and environment as well as gene–environment interactions in human health, with a particular emphasis on diet, body composition and metabolic health 1–12 …”