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.
Curr Dev Nutr
; 8(2): 102075, 2024 Feb.
Article
en En
| MEDLINE
| ID: mdl-38351975
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 11 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.
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Banco de datos:
MEDLINE
Tipo de estudio:
Clinical_trials
/
Observational_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Curr Dev Nutr
Año:
2024
Tipo del documento:
Article
País de afiliación:
China