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Choline intake and genetic polymorphisms influence choline metabolite concentrations in human breast milk and plasma.

ABSTRACT: Choline is essential for infant nutrition, and breast milk is a rich source of this nutrient. Common single nucleotide polymorphisms (SNPs) change dietary requirements for choline intake.The aim of this study was to determine whether total choline intake and/or SNPs influence concentrations of choline and its metabolites in human breast milk and plasma.We gave a total of 103 pregnant women supplemental choline or a placebo from 18 wk gestation to 45 d postpartum and genotyped the women for 370 common SNPs. At 45 d postpartum, we measured choline metabolite concentrations in breast milk and plasma and assessed the dietary intake of choline by using a 3-d food record.On average, lactating women in our study ate two-thirds of the recommended intake for choline (Adequate Intake = 550 mg choline/d). Dietary choline intake (no supplement) correlated with breast-milk phosphatidylcholine and plasma choline concentrations. A supplement further increased breast-milk choline, betaine, and phosphocholine concentrations and increased plasma choline and betaine concentrations. We identified 5 SNPs in MTHFR that altered the slope of the intake-metabolite concentration relations, and we identified 2 SNPs in PEMT that shifted these curves upward. Individuals who shared sets of common SNPs were outliers in plots of intake-metabolite concentration curves; we suggest that these SNPs should be further investigated to determine how they alter choline metabolism.Total intake of choline and genotype can influence the concentrations of choline and its metabolites in the breast milk and blood of lactating women and thereby affect the amount of choline available to the developing infant. This study was registered at clinicaltrials.gov as NCT00678925.

SUBMITTER: Fischer LM

PROVIDER: S-EPMC2904035 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Choline intake and genetic polymorphisms influence choline metabolite concentrations in human breast milk and plasma.

Fischer Leslie M LM da Costa Kerry Ann KA Galanko Joseph J Sha Wei W Stephenson Brigitte B Vick Julie J Zeisel Steven H SH

The American journal of clinical nutrition 20100609 2

<h4>Background</h4>Choline is essential for infant nutrition, and breast milk is a rich source of this nutrient. Common single nucleotide polymorphisms (SNPs) change dietary requirements for choline intake.<h4>Objective</h4>The aim of this study was to determine whether total choline intake and/or SNPs influence concentrations of choline and its metabolites in human breast milk and plasma.<h4>Design</h4>We gave a total of 103 pregnant women supplemental choline or a placebo from 18 wk gestation ...[more]

PMID: 20534746

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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:Tenofovir (TFV) is eliminated by renal excretion, which is mediated through multidrug-resistant protein 2 (MRP2) and MRP4, encoded by ABCC2 and ABCC4, respectively. Genetic polymorphisms of these transporters may affect the plasma concentrations of tenofovir. Therefore, the aim of this study was to investigate the influence of genetic and nongenetic factors on tenofovir plasma concentrations. A cross-sectional study was performed in Thai HIV-infected patients aged ≥18 years who had been receiving tenofovir disoproxil fumarate at 300 mg once daily for at least 6 months. A middose tenofovir plasma concentration was obtained. Multivariate analysis was performed to investigate whether there was an association between tenofovir plasma concentrations and demographic data, including age, sex, body weight, estimated glomerular filtration rate (eGFR), hepatitis B virus coinfection, hepatitis C virus coinfection, duration of tenofovir treatment, concomitant use of ritonavir-boosted protease inhibitors, and polymorphisms of ABCC2 and ABCC4. A total of 150 Thai HIV-infected patients were included. The mean age of the patients was 43.9 ± 7.2 years. The mean tenofovir plasma concentration was 100.3 ± 52.7 ng/ml. In multivariate analysis, a low body weight, a low eGFR, the concomitant use of ritonavir-boosted protease inhibitors, and the ABCC4 4131T → G variation (genotype TG or GG) were independently associated with higher tenofovir plasma concentrations. After adjusting for weight, eGFR, and the concomitant use of ritonavir-boosted protease inhibitors, a 30% increase in the mean tenofovir plasma concentration was observed in patients having the ABCC4 4131 TG or GG genotype. Both genetic and nongenetic factors affect tenofovir plasma concentrations. These factors should be considered when adjusting tenofovir dosage regimens to ensure the efficacy and safety of a drug. (This study has been registered at ClinicalTrials.gov under registration no. NCT01138241.).

Dataset Information

Choline intake and genetic polymorphisms influence choline metabolite concentrations in human breast milk and plasma.

Publications

Choline intake and genetic polymorphisms influence choline metabolite concentrations in human breast milk and plasma.

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