Dataset Information

The Mediating Effect of the Choline-to-Betaine Ratio on the Association Between PEMT rs7946 and Digestive System Cancer: A Nested Case-Control Study in a Chinese Population.

ABSTRACT:

Background

The enzyme phosphatidylethanolamine N-methyltransferase (PEMT) is responsible for synthesizing phosphatidylcholine by methylating phosphatidylethanolamine. We hypothesized that a polymorphism of the PEMT gene, rs7946, is involved in carcinogenesis.

Objectives

We aimed to investigate the relationship between PEMT rs7946 and digestive system cancer and examine possible effect modifiers and mediators.

Methods

We conducted a nested, case-control study within the China H-type Hypertension Registry Study, including 751 cases and 1:1 matched controls. To assess the association of PEMT rs7946 and digestive system cancer, we estimated odds ratios with 95% confidence intervals (CIs) using conditional logistic regression. We used the bootstrap test to examine the potential mediating effects of related metabolites.

Results

Our results revealed that wild-type homozygous CC genotype carriers of PEMT rs7946 had a significantly increased risk [odds ratio (OR): 1.31; 95% CI: 1.04, 1.66; P = 0.023] compared with the TT/CT combined genotypes. The effect was found to be more pronounced in individuals with a lower choline-to-betaine ratio (<0.412, P-interaction = 0.021). Furthermore, the mediation analysis indicated that the choline-to-betaine ratio played a significant role in mediating 13.55% of the association between PEMT rs7946 and digestive system cancer (P = 0.018).

Conclusions

Our study suggested that PEMT rs7946 may affect risk of digestive system cancer through direct and indirect pathways, and the choline-to-betaine ratio may partially mediate the indirect effect.This trial was registered at Chinese Clinical Trial Registry as ChiCTR1800017274.

SUBMITTER: He Q

PROVIDER: S-EPMC10862518 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Mediating Effect of the Choline-to-Betaine Ratio on the Association Between <i>PEMT</i> rs7946 and Digestive System Cancer: A Nested Case-Control Study in a Chinese Population.

He Qiangqiang Q Wei Yaping Y Zhu Hehao H Song Yun Y Chen Ping P Wang Binyan B Shi Hanping H Qin Peiwu P

Current developments in nutrition 20240104 2

<h4>Background</h4>The enzyme phosphatidylethanolamine N-methyltransferase (<i>PEMT</i>) is responsible for synthesizing phosphatidylcholine by methylating phosphatidylethanolamine. We hypothesized that a polymorphism of the <i><i>PEMT</i></i> gene, rs7946, is involved in carcinogenesis.<h4>Objectives</h4>We aimed to investigate the relationship between <i>PEMT</i> rs7946 and digestive system cancer and examine possible effect modifiers and mediators.<h4>Methods</h4>We conducted a nested, case-c ...[more]

PMID: 38351975

Similar Datasets

Project description:Abstract Objectives Choline-metabolizing genetic variation may interact with choline intake on fetal programming and pregnancy outcome. This case-control study aims to explore the association of maternal choline consumption and phosphatidylethanolamine N-methyltransferase (PEMT) gene polymorphism rs7946 with incident preterm birth. Methods 165 Chinese Han women with preterm delivery and 165 Chinese Han women with term delivery were recruited in Shanghai, China. Dietary choline intake during pregnancy was assessed using a validated food frequency questionnaire. Additionally, DNA samples were genotyped for PEMT rs7946 (G5465A) by a real-time polymerase chain reaction method with plasma homocysteine (Hcy) levels measured by an enzymatic cycling method. Odds ratio (OR) and 95% CI were estimated using unconditional logistic regression with adjustment of the covariates which were selected based on a comparison of social-democratic and clinical characteristics between two groups. Results There was a significant interaction between maternal choline intake and PEMT rs7946 (P for interaction = 0.04), where the AA genotype carriers who consumed the energy-adjusted choline <255.01 mg/d had an adjusted OR for preterm birth of 3.75 (95% CI 1.24–11.35), compared to those with GG genotype and choline intake >255.01 mg/d during pregnancy. Additionally, the highest plasma Hcy was found in the cases with AA genotype and choline consumption <255.01 mg/d (P < 0.001). The AA genotype was also associated with a greater risk of preterm birth among the women when their plasma Hcy is at the highest tertile level (AA vs. GA + GG: adjusted OR = 1.56, 95% CI 1.02–2.88). Conclusions The AA genotype of PEMT rs7946 may be associated with increased preterm birth in these Chinese Han women with low choline intake during pregnancy. The observed association may be partially explained by mechanisms related to the increasing Hcy level induced by PEMT rs7946 gene polymorphism. This study was registered at ClinicalTrials.gov (#NCT02841813). Funding Sources The Danone Nutrition Research and Education Grant (DIC2017–09); Research Project of Shanghai University of Traditional Chinese Medicine (2019LK042).

Project description:Trimethylamine N-oxide (TMAO) and its precursors, including choline, betaine, and L-carnitine, are gut microbiota-related metabolites associated with the risk of obesity. We aimed (1) to comprehensively examine whether the changes in plasma TMAO and its precursors induced by lifestyle intervention are associated with the improvements in plasma metabolic parameters; and (2) to identify the fecal microbiome profiles and nutrient intakes associated with these metabolites and metabolic index. Data from 40 participants (obese children and adolescents) having the plasma metabolites data related to the changes in BMI z-scores after 6-month lifestyle intervention were analyzed. In this study, we observed that choline and the betaine-to-choline ratio (B/C) showed different patterns depending on the changes in BMI z-scores by the response to lifestyle intervention. During the 6 months, an increase in choline and a decrease in B/C were observed in non-responders. We also found that changes in choline and B/C were associated with the improvements in plasma lipid levels. Individuals who showed reduced choline or increased B/C from the baseline to 6 months had a significant decrease in LDL-cholesterol over 6 months compared to those with increased choline or decreased B/C, respectively. In addition, the increase in choline or decrease in B/C was associated with the increase in plasma triglycerides. The distribution of gut microbiota belonging to the Firmicutes, such as Clostridia, Clostridiales, Peptostreptococcaceae, Romboutsia, and Romboutsia timonensis was altered to be lower during the 6 months both as choline decreased and B/C increased. Moreover, the decrease in choline and the increase in B/C were associated with reduced fat intake and increased fiber intake after the 6-month intervention. Finally, lower abundance of Romboutsia showed the association with lower LDL-cholesterol and higher intake of fiber. In summary, we demonstrated that reduced choline and increased B/C by lifestyle intervention were associated with the improvements of LDL-cholesterol and triglycerides, low-fat and high-fiber intakes, and low abundance of Firmicutes. These indicate that changes to circulating choline and B/C could predict individuals' changes in metabolic compositions in response to the lifestyle intervention.