Neural tube defects (NTDs) are a spectrum of severe congenital malformations of fusion failure of the neural tube during early embryogenesis. Evidence on aberrant DNA methylation in NTD development remains scarce, especially when exposure to environmental pollutant is taken into consideration. DNA methylation profiling was quantified using the Infinium HumanMethylation450 array in neural tissues from 10 NTD cases and 8 non-malformed controls (stage 1). Subsequent validation was performed using a Sequenom MassARRAY system in neural tissues from 20 NTD cases and 20 non-malformed controls (stage 2). Correlation analysis of differentially methylated CpG sites in fetal neural tissues and polycyclic aromatic hydrocarbons concentrations in fetal neural tissues and maternal serum was conducted. Differentially methylated CpG sites of neural tissues were further validated in fetal mice with NTDs induced by benzo(a)pyrene given to pregnant mice. Differentially hypermethylated CpG sites in neural tissues from 17 genes and 6 pathways were identified in stage 1. Subsequently, differentially hypermethylated CpG sites in neural tissues from 6 genes (BDKRB2, CTNNA1, CYFIP2, MMP7, MYH2, and TIAM2) were confirmed in stage 2. Correlation analysis showed that methylated CpG sites in CTNNA1 and MYH2 from NTD cases were positively correlated to polycyclic aromatic hydrocarbon level in fetal neural tissues and maternal serum. The correlation was confirmed in NTD-affected fetal mice that were exposed to benzo(a)pyrene in utero. In conclusion, hypermethylation of the CTNNA1 and MYH2 genes in tight junction pathway is associated with the risk for NTDs, and the DNA methylation aberration may be caused by exposure to benzo(a)pyrene.

No abstract

Daily supplementation with a low-dose of B vitamins for 12 months reduced FRS, particularly in healthy elderly subjects with a folate deficiency. These reduced effects declined after supplementation cessation, indicating a need for persistent supplementation to maintain the associated benefits.

Plasma folate levels among pregnant Chinese women increased dramatically after the nation-wide folic acid supplementation program in both rural and urban areas, and in populations of high and low NTD prevalence. The nation-wide program should have a component to ensure that supplementation begins before pregnancy.

A large number of non-synonymous single-nucleotide polymorphisms (nsSNPs) have been found in human genome, but there is poor knowledge on the relationship between the genotype and phenotype of these nsSNPs. Human ATP-binding cassette (ABC) transporters are able to transport a number of important substrates including endogenous and exogenous compounds. This study aimed to predict the phenotypical impact of nsSNPs of human ABC transporter genes, and the predicted results were further validated by reported phenotypical data from site-directed mutagenesis and clinical genetic studies. One thousand and six hundred thirty-two nsSNPs were found from 49 human ABC transporter genes. Using the PolyPhen and SIFT algorithms, 41.8-53.6% of nsSNPs in ABC transporter genes were predicted to have an impact on protein function. The prediction accuracy was up to 63-85% when compared with known phenotypical data from in vivo and in vitro studies. There was a significant concordance between the prediction results using SIFT and PolyPhen. Of nsSNPs predicted as deleterious, the prediction scores by SIFT and PolyPhen were significantly related to the number of nsSNPs with known phenotypes confirmed by experimental and human studies. The amino acid substitution variants are supposed to be the pathogenetic basis of increased susceptibility to certain diseases with Mendelian or complex inheritance, altered drug resistance and altered drug clearance and response. Predicting the phenotypic consequence of nsSNPs using computational algorithms may provide a better understanding of genetic differences in susceptibility to diseases and drug response. The prediction of nsSNPs in human ABC transporter genes would be useful hints for further genotype-phenotype studies.

We concluded that CRP increased with gestational age among healthy Chinese women who delivered healthy infants. Am. J. Hum. Biol. 28:574-579, 2016. © 2016 Wiley Periodicals, Inc.

Universal prenatal daily iron-folic acid (IFA) and multiple micronutrient (MM) supplements are recommended to reduce the risk of low birth weight, maternal anemia, and iron deficiency (ID) during pregnancy, but the evidence of their effect on iron status among women with mild or no anemia is limited. The aim of this study was to describe the iron status [serum ferritin (SF), serum soluble transferrin receptor (sTfR), and body iron (BI)] before and after micronutrient supplementation during pregnancy. We examined 834 pregnant women with hemoglobin > 100 g/L at enrollment before 20 wk of gestation and with iron measurement data from a subset of a randomized, double-blind trial in China. Women were randomly assigned to take daily 400 μg of folic acid (FA) (control), FA plus 30 mg of iron, or FA, iron, plus 13 additional MMs provided before 20 wk of gestation to delivery. Venous blood was collected in this subset during study enrollment (before 20 wk of gestation) and 28-32 wk of gestation. We found that, at 28-32 wk of gestation, compared with the FA group, both the IFA and MM groups had significantly lower prevalence of ID regardless of which indicator (SF, sTfR, or BI) was used for defining ID. The prevalence of ID at 28-32 wk of gestation for IFA, MM, and FA were 35.3%, 42.7%, and 59.6% by using low SF, 53.6%, 59.9%, and 69.9% by using high sTfR, and 34.5%, 41.2%, and 59.6% by using low BI, respectively. However, there was no difference in anemia prevalence (hemoglobin < 110 g/L) between FA and IFA or MM groups. We concluded that, compared with FA alone, prenatal IFA and MM supplements provided to women with no or mild anemia improved iron status later during pregnancy but did not affect perinatal anemia. This trial was registered at clinicaltrials.gov as NCT00137744.

Adequate docosahexaenoic acid (DHA) is essential for the optimal growth and development of the fetus. Maternal DHA content fluctuates during pregnancy. The correlation of DHA content with dietary intake might be varied over the course of pregnancy. We aimed to compare the dietary DHA intake, estimated by a DHA-specific semiquantitative food frequency questionnaire (FFQ) against its blood content, among mid- and late-term pregnant women. A total of 804 Chinese pregnant women completed the tailored FFQ and provided fasting venous blood samples. Dietary DHA intake (mg/day) in the previous month was calculated from the FFQ using Chinese Food Composition Table. DHA concentrations (weight percent of total fatty acids) in plasma and erythrocytes were measured by capillary gas chromatography. Spearman correlation coefficients (rs) between DHA intake and its relative concentrations were calculated. After adjustment for maternal age, pre-pregnancy body mass index, stage of pregnancy, parity, education level, ethnicity, and annual family income per capita, the correlation coefficients of DHA intake with its concentrations in plasma and erythrocytes were 0.35 and 0.33, respectively (p < 0.001). The correlations were relatively stronger among women in late pregnancy (rs = 0.44 in plasma and 0.39 in erythrocytes) than those in mid-pregnancy (rs = 0.25 and 0.26). The significant correlations were consistently observed in subgroups stratified by regions, except for erythrocytes in women living in a coastland area. Multiple regression analyses also indicated significant positive linear correlations between DHA intake and its plasma or erythrocytes concentrations (p < 0.001). In conclusion, dietary DHA intake, estimated by the FFQ, was positively correlated with its concentrations in plasma and erythrocytes in Chinese pregnant women, especially for women in late pregnancy, with the exception of the erythrocytes of those living in a coastland area.