Dietary Choline Intake During Pregnancy and PEMT rs7946 Polymorphism on Risk of Preterm Birth: A Case-Control Study

Abstract

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).