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Baltimore Highlands, MD, United States

Liu X.,Northwestern University | Chen Q.,Northwestern University | Tsai H.-J.,Northwestern University | Tsai H.-J.,National Health Research Institute | And 16 more authors.
Environmental and Molecular Mutagenesis | Year: 2014

Maternal obesity is associated with a variety of common diseases in the offspring. One possible underlying mechanism could be maternal obesity induced alterations in DNA methylation. However, this hypothesis is yet to be tested. We performed epigenomic mapping of cord blood among 308 Black mother-infant pairs delivered at term at the Boston Medical Center using the Illumina HumanMethylation27 BeadChip. Linear regression and pathway analyses were conducted to evaluate the associations between DNA methylation levels and prepregnancy maternal BMI (<25, 25-30, ≥30 kg/m2). The methylation levels of 20 CpG sites were associated with maternal BMI at a significance level of P-value <10-4 in the overall sample, and boys and girls, separately. One CpG site remained statistically significant after correction for multiple comparisons (FDR corrected P-value = 0.04) and was annotated to a potential cancer gene, ZCCHC10. Some of the other CpG site annotated genes appear to be critical to the development of cancers and cardiovascular diseases (i.e., WNT16, C18orf8, ANGPTL2, SAPCD2, ADCY3, PRR16, ERBB2, DOK2, PLAC1). Significant findings from pathway analysis, such as infectious and inflammatory and lipid metabolism pathways, lends support for the potential impact of maternal BMI on the above stated disorders. This study demonstrates that prepregnancy maternal BMI might lead to alterations in offspring DNA methylation in genes relevant to the development of a range of complex chronic diseases, providing evidence of trans-generational influence on disease susceptibility via epigenetic mechanism. © 2013 Wiley Periodicals, Inc. Source

Zong G.,Harvard University | Grandjean P.,Harvard University | Grandjean P.,University of Southern Denmark | Wang X.,Center on the Early Life Origins of Disease | Sun Q.,Harvard University
Environmental Research | Year: 2016

Objective Lactation may help curb diabetes risk and is also known as an excretion route for some environmental pollutants. We evaluated associations of lifetime lactation history with serum concentrations of persistent organic pollutants (POPs) in the National Health and Nutrition Examination Survey 1999–2006, and examined whether potentially diabetogenic POPs account for associations between lactation and diabetes. Research design and methods Among 4479 parous women, breastfeeding history was defined as the number of children breastfed ≥1 month. Diabetes was identified by self-report or hemoglobin A1c >6.5%. Twenty-four POPs were measured in serum among subsamples of 668 to 1073 participants. Results Compared with women without lactation history, odds ratios (95% confidence intervals) of having diabetes among those with 1–2 and ≥3 lactation periods were 0.83(0.61, 1.13) and 0.63(0.44, 0.91; P trend=0.03). Lifetime lactation history was inversely associated with serum concentrations of 17 out of the 24 organochlorine pesticides, polychlorinated biphenyl congeners (PCBs), and perfluoroalkyl substances (Ptrend<0.05). Comparing the ≥3 lactations group with women without a lactation history, the relative reduction of POPs ranged from 12% (PCB-196) to 30% (oxychlordane). The inverse association between lactation and diabetes was slightly attenuated after adjustment for POPs. Age-stratified analyses showed that the inverse association between lactation periods and serum POP concentrations was observed primarily among participants <60 years, whereas age did not significantly modify the association between lactation history and diabetes prevalence. Conclusion Crudely-classified lifetime lactation history was inversely associated with concurrent serum POP concentrations and diabetes prevalence. Prospective studies are needed to clarify how lactation could complement diabetes prevention through decreasing the POP body burdens. © 2016 Elsevier Inc. Source

Guo X.,Wenzhou University | Guo X.,Inner Mongolia University | Cui H.,Wenzhou University | Zhang H.,Wenzhou University | And 12 more authors.
Medicine (United States) | Year: 2015

Although previous reports have linked DNA damage with both transmissions across generations as well as our own survival, it is unknown how to reverse the lesion. Based on the data from a Randomized, Double-blind, Placebo Controlled Clinical Trial, this study aimed to assess the efficacy of folic acid supplementation (FAS) on DNA oxidative damage reversal. In this randomized clinical trial (RCT), a total of 450 participants were enrolled and randomly assigned to 3 groups to receive folic acid (FA) 0.4 mg/day (low-FA), 0.8 mg/day (high-FA), or placebo (control) for 8 weeks. The urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and creatinine (Cr) concentration at pre-and post-FAS were measured with modified enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. A multivariate general linear model was applied to assess the individual effects of FAS and the joint effects between FAS and hypercholesterolemia on oxidative DNA damage improvement. This clinical trial was registered with ClinicalTrials.gov, number NCT02235948. Of the 438 subjects that received FA fortification or placebo, the median (first quartile, third quartile) of urinary 8-OHdG/Cr for placebo, low-FA, and high-FA groups were 58.19 (43.90, 82.26), 53.51 (38.97, 72.74), 54.73 (39.58, 76.63) ng/mg at baseline and 57.77 (44.35, 81.33), 51.73 (38.20, 71.30), and 50.65 (37.64, 76.17) ng/mg at the 56th day, respectively. A significant decrease of urinary 8-OHdG was observed after 56 days FA fortification (P < 0.001). Compared with the placebo, after adjusting for some potential confounding factors, including the baseline urinary 8-OHdG/Cr, the urinary 8-OHdG/Cr concentration significantly decreased after 56 days FAS [β (95% confidence interval) =-0.88 (-1.62,-0.14) and P = 0.020 for low-FA; and β (95% confidence interval) =-2.68 (-3.42,-1.94) and P < 0.001 for high-FA] in a dose-response fashion (P trend < 0.001). Test of interaction between hypercholesterolemia and FA supplementation on urinary 8-OHdG reduction was significant (P = 0.001). The present study demonstrates that FA fortification is independently linked to the reduction of urinary 8-OHdG/Cr in a dose-related pattern, which suggests that FA is beneficial to protect against oxidative damage to DNA. This effect is apparently stronger in those with hypercholesterolemia. The authors provide a new insight into the prevention and reversal of oxidative DNA damage. © 2015 Wolters Kluwer Health, Inc. Source

Hong X.,Center on the Early Life Origins of Disease | Caruso D.,Center on the Early Life Origins of Disease | Kumar R.,Childrens Memorial Hospital | Liu R.,Northwestern University | And 5 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2012

Background There are no available clinical tests that can accurately predict peanut allergy (PA) and/or anaphylaxis. This study is aimed at evaluating whether the component-resolved diagnostic (CRD) IgE and IgG4 tests can (i) distinguish PA from asymptomatic peanut sensitization (PS) and (ii) differentiate anaphylactic from nonanaphylactic PA. Methods This study included 20 nonatopic controls, 58 asymptomatically peanut-sensitized children, 55 nonanaphylactic, and 53 anaphylactic PA cases from the Chicago Food Allergy Study. IgE and IgG4 to 103 allergens were measured using the ImmunoCAP ISAC technology and were compared among each group of children. The random forest test was applied to estimate each allergen's ability to predict PA and/or peanut anaphylaxis. Results Peanut allergy cases (with or without anaphylaxis) had significantly higher IgE reactivity to Ara h 1-3 (peanut allergens) and Gly m 5-6 (soy allergens) than asymptomatically sensitized children (P < 0.00001). Similar but more modest relationships were found for IgG4 to Ara h 2 (P < 0.01). IgE to Ara h 2 was the major contributor to accurate discrimination between PA and asymptomatic sensitization. With an optimal cutoff point of 0.65 ISU-E, it conferred 99.1% sensitivity, 98.3% specificity, and a 1.2% misclassification rate in the prediction of PA, which represented a higher discriminative accuracy than IgE to whole peanut extract (P = 0.008). However, none of the IgE and/or IgG4 tests could significantly differentiate peanut anaphylaxis from nonanaphylactic PA. Conclusions IgE to Ara h 2 can efficiently differentiate clinical PA from asymptomatic PS, which may represent a major step forward in the diagnosis of PA. © 2012 John Wiley & Sons A/S. Source

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