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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).

SUBMITTER: Zhu J

PROVIDER: S-EPMC7257329 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Project description:Abstract Objectives Adequate intake of dietary choline, an essential nutrient, is pivotal for an optimal pregnant outcome and fetal programming, which may be affected by choline-metabolising genetic polymorphisms. This case-control study aims to investigate the interaction between choline intake during pregnancy and genetic polymorphisms in choline dehydrogenase (CHDH) and betaine-homocysteine methyltransferase (BHMT) on preterm birth risk among Chinese women. Methods 129 women with preterm delivery and 141 parturients with full-term delivery were recruited respectively at Xinhua Hospital, Shanghai between March 2016 and July 2018. Dietary choline intake during pregnancy was assessed by a validated food frequency questionnaire, genotyping was conducted for CHDH (G233C, rs12676) and BHMT (G742A, rs3733890), and plasma homocysteine (Hcy) levels were assayed. X2 test, Kruskal-Wallis H test, and unconditional logistic regression were conducted for statistical analysis. Results Neither choline intake during pregnancy nor CHDH rs12676 or BHMT rs3733890 alone was significantly correlated with the incidence of preterm birth after adjustment for total energy intake, folate consumption, delivery age, occupation, prepregnancy BMI, parity, hypertensive disorders of pregnancy, and gestational diabetes. However, significant interactions were observed between maternal choline intake during pregnancy and CHDH rs12676 (Pinteraction = 0.023) or BHMT rs373389 (Pinteraction = 0.045) on preterm delivery risk after adjusting for multiple confounding variables. Plasma Hcy level was about 38% higher in the case women carrying CC genotype of CHDH rs12676 who consumed less choline than the median during pregnancy, compared to the control women with GG genotype who had more choline intake than the median level (P<0.001). Similarly, the case women carrying AA genotype of BHMT rs373389 who consumed less choline than the median showed about 21% higher Hcy levels, compared with the control women with GG genotype who had more choline intake than the median level (P<0.001). Conclusions Our results indicate that genetic polymorphism of CHDH rs12676 or BHMT rs3733890 may interact with maternal choline intake, which may modify preterm birth risk among Chinese women partially through the disturbance in choline metabolism. This study was registered at clinic trails (No. NCT02841813). Funding Sources This study was supported by the Danone Nutrition Research and Education Grant (DIC2017-09).

Project description:BackgroundPrevious studies have yielded inconsistent results on the association between maternal dietary protein intake and birth weight. Moreover, little is known about the effects of dietary protein intake from different sources on fetal growth. This study aimed to investigate the associations of different dietary protein sources (total protein, animal protein, plant protein, and major dietary protein sources) during pregnancy with birth weight and the related adverse birth outcomes.Methods7310 women were recruited using a stratified multistage random sampling method at 0-12 months (median: 3; 10-90th percentile: 0-7) after delivery in Shaanxi, China. Maternal diets were gathered by a validated FFQ and other characteristics were collected by a standard questionnaire. Multilevel linear or logistic regression models were used to estimate birth weight changes or ORs (95% CIs) for adverse birth outcomes associated with different dietary protein sources during pregnancy.ResultsThe mean percentage of energy from total protein was 11.4% (SD 2.2), with only 27.4% of total protein derived from animal protein. Per 3% increase in energy from total protein, animal protein, and dairy protein was associated with birth weight increases of 19.4 g (95% CI 6.0-32.9), 20.6 g (4.8-36.5), and 18.2 g (4.7-31.7), respectively. Per 3% increase in energy from total protein, animal protein, and dairy protein was also associated with lower risks of low birth weight (LBW) (total protein: OR = 0.78, 95% CI 0.64-0.94; animal protein: 0.79, 0.65-0.96; dairy protein: 0.71, 0.56-0.91), small for gestational age (SGA) (total protein: 0.88, 0.79-0.98; animal protein: 0.87, 0.78-0.97; dairy protein: 0.81, 0.68-0.96), and intrauterine growth retardation (IUGR) (total protein: 0.84, 0.72-0.98; animal protein: 0.86, 0.75-0.98; dairy protein: 0.78, 0.66-0.92). We observed no associations of plant protein and other major dietary protein sources with birth weight and the above birth outcomes. The results did not change when maternal protein was substituted for fat or carbohydrate.ConclusionsAmong Chinese pregnant women with low intake of protein, higher intake of dietary protein, in particular animal protein and dairy protein, is associated with higher birth weight and lower risks of LBW, SGA, and IUGR.

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

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