Search

Phthalates (PAEs) are synthetic compounds extensively employed in consumer products. Blood pressure (BP) in children can vary, the degree of visit-to-visit BP variability (VVV) is at least partially independent of BP. The interactions between PAEs exposure, pubertal-related genetic susceptibility and lifestyles on childhood VVV are not investigated. This study utilized data from a cohort collected from Oct 2017–2020 in Xiamen, China. Seven urine PAE metabolites were measured. The long-term VVV was characterized employing the standard deviation (SD) and average real variability. We constructed a genetic risk score (GRS) of pubertal-related genes and healthy lifestyle scores. Exposed to high levels of mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (OR=1.43, 95 %CI=1.07, 1.92) and mono-2-ethyl-5-oxohexyl phthalate (OR=1.36, 95 % CI=1.01, 1.83) was related to increased SBP-SD, and the OR for high SBP-SD related to high GRS was 1.38 (95 % CI=1.02, 1.85). Compared to participants who had low GRS and low MEHHP exposure, participants exhibiting high GRS and MEHHP levels were more likely to experience high SBP-SD (OR=2.00, P

Summary: Background: The prevalence of metabolic-associated steatotic liver disease (MASLD) is rising precipitously among children, particularly in regions or countries burdened with high prevalence of obesity. However, identifying those at high risk remains a significant challenge, as the majority do not exhibit distinct symptoms of MASLD. There is an urgent need for a widely accepted non-invasive predictor to facilitate early disease diagnosis and management of the disease. Our study aims to 1) evaluate and compare existing predictors of MASLD, and 2) develop a practical screening strategy for children, tailored to local prevalence of obesity. Methods: We utilized a school-based cross-sectional survey in Beijing as the training dataset to establish predictive models for screening MASLD in children. An independent school-based study in Ningbo was used to validate the models. We selected the optimal non-invasive MASLD predictor by comparing logistic regression model, random forest model, decision tree model, and support vector machine model using both the Beijing and Ningbo datasets. This was followed by serial testing using the best performance index we identified and indices from previous studies. Finally, we calculated the potential MASLD screening recommendation categories and corresponding profits based on national and subnational obesity prevalence, and applied those three categories to 200 countries according to their obesity prevalence from 1990 to 2022. Findings: A total of 1018 children were included (NBeijing = 596, NNingbo = 422). The logistic regression model demonstrated the best performance, identifying the waist-to-height ratio (WHtR, cutoff value ≥0.48) as the optimal noninvasive index for predicting MASLD, with strong performance in both training and validation set. Additionally, the combination of WHtR and lipid accumulation product (LAP) was selected as an optimal serial test to improve the positive predictive value, with a LAP cutoff value of ≥668.22 cm × mg/dL. Based on the obesity prevalence among 30 provinces, three MASLD screening recommendations were proposed: 1) “Population-screening-recommended”: For regions with an obesity prevalence ≥12.0%, where MASLD prevalence ranged from 5.0% to 21.5%; 2) “Resources-permitted”: For regions with an obesity prevalence between 8.4% and 12.0%, where MASLD prevalence ranged from 2.3% to 4.4%; 3) “Population-screening-not-recommended”: For regions with an obesity prevalence

Abstract Background Myopia and obesity in children and adolescents have become serious public health problems that endanger public health, especially in China. Unhealthy lifestyle behaviors are environmental drivers of both myopia and obesity. This protocol describes a study to evaluate the effectiveness of “22510SS”, that is 2 h of daytime outdoor activities (‘2’); Limit screen time to no more than 2 h per day (‘2’); Consume at least 5 servings of fruits and vegetables daily (‘5’); Attain 1 h of physical activity daily (‘1’); Consume 0 sugar-sweetened beverages (‘0’); Reasonable sleep duration (‘S’); Regular supervision (‘S’). A school-based, multifaceted intervention strategy for myopia and obesity prevention, and to assess and explore the implementation of “22510SS” with regards to acceptability, feasibility, adoption, usage and maintenance. Methods and analysis This study aims to develop a comprehensive intervention strategy "22510SS" based on the socio-ecological model, and A two-arm cluster randomized trial with a parallel-group of a 1:1 allocation ratio in 36 primary and secondary schools to test its evidence-based intervention programs on the effects and implementation of myopia and obesity epidemics in children and adolescents in grades 4 and 7. The primary outcomes will include differences in visual acuity, body mass index, outdoor activity indicators, screen time, fruit and vegetable intake, high-quality protein intake, sugar-sweetened beverage intake, sleep duration, and level of monitoring among children and adolescents. Secondary outcomes will assess the acceptability, feasibility, uptake, use, and maintenance of the intervention. Effects on the primary and secondary outcomes will be analyzed using linear and logistic regression analyses, as well as difference-in-difference analysis, taking into account cluster effects and possible confounding factors. Process assessments will also be conducted through quantitative and qualitative analyses, including acceptability, feasibility, gender, adoption, implementation, and sustainability. Discussion This study will evaluate the effectiveness of “22510SS” and examine its implementation in the school-based network nesting family and clinic. Following this intervention study, the integrated intervention program focused on myopia and obesity among children and adolescents have great potential to be implemented in China to promote and support healthy lifestyle behavior change and reduce the risk of myopia and obesity in children and adolescents. Trial registration NCT05275959. Registered 23 Mach 2022.

Abstract Background The single nucleotide polymorphisms (SNPs) in the fatty acid desaturases and elongases might associate with the endogenous synthesis of polyunsaturated fatty acids (PUFAs). However, the related epidemiological evidence is still conflicting. So we aimed to clearly evaluate the interactions between maternal DHA-rich n-3 PUFAs supplementation and the known 26 SNPs on the profiles of PUFAs in the colostrum using a Chinese birth cohort. Methods Totally, 1050 healthy mother-infant pairs were enrolled in this study at gestational 6–8 weeks when they established their pregnancy files at Fuxing Hospital affiliated to Capital Medical University in Beijing from January to December 2018. Meanwhile, their venous blood samples were obtained for DNA extraction to detect the genotypes of SNPs in the Fads1, Fads2, Fads3, Elovl2 and Elovl5 using the Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry. Then the colostrum samples were collected to determine the profiles of PUFAs by gas chromatography. Results Maternal DHA-rich n-3 PUFAs supplementation from the early and middle pregnancy could reduce the infant BMI at birth, and impact the profiles of PUFAs in the colostrum, as higher n-3 PUFAs (EPA, DHA, DHA/ALA and DHA/EPA), lower n-6 PUFAs (AA and AA/LA) and ∑-6/n-3ΣPUFAs. Moreover, there were significant correlations between multiple SNPs and the profiles of n-6 PUFAs (rs76996928 for LA, rs174550, rs174553 and rs174609 for AA, rs174550 and rs76996928 for AA/LA) and n-3 PUFAs in the colostrum (rs174448, rs174537, rs174550, rs174553, rs174598, rs3168072, rs174455 and rs174464 for ALA, rs174550, rs174553 and rs174598 for EPA, rs174455 and rs174464 for DHA, rs174448 and rs3168072 for DHA/EPA) using the multiple linear regressions by adjusting the maternal age, gestational week, mode of delivery, infant sex and BMI at birth, and all these above significant SNPs had the cumulative effects on the profiles of PUFAs. Furthermore, the pairwise comparisons also showed the meaningful interactions between maternal DHA-rich n-3 PUFAs supplementation and related genotypes of SNPs (rs76996928 for LA, rs174598 for EPA, rs174448 for DHA and DHA/EPA) on the contents of PUFAs in the colostrum. Conclusions Results from this birth cohort study proved that the pregnant women with the following SNPs such as Fads3 rs174455 T, Fads3 rs174464 A and Fads1 rs174448 G alleles should pay more attention on their exogenous DHA supplementation from the early and middle pregnancy for the blocked endogenous synthesis. Trial registration: This study was approved by the Ethics Committee of Beijing Pediatric Research Institution, Beijing Children’s Hospital affiliated to Capital Medical University (2016–08), which was also registered at the website of http://www.chictr.org.cn/showproj.aspx?proj=4673 (No: ChiCTR-OCH-14004900).

Abstract Background The associations of famine exposure with diabetes risk in adulthood are still unclear. This study aimed to explore the association between famine exposure in early life and risk of diabetes in adulthood. Methods A total of 4138 subjects were selected from the data of the China Health and Retirement Longitudinal Study (CHARLS) 2011–2012. Diabetes was diagnosed as fasting plasma glucose (FPG) ≥7.0 mmol/L, glycated haemoglobin (HbA1C) > 6.5%, or self-reported diabetes. Birthdates of subjects were used to categorize famine exposure groups. The association of fetal-stage famine exposure with diabetes risk in adults was assessed using logistics regression model. Results The prevalence of diabetes in the non-exposed, fetal-stage exposed, infant-stage exposed, and preschool-stage exposed groups were 9.0, 13.6, 12.7 and 10.8%, respectively. Compared with the age-balanced control group, the fetal-stage exposed group was associated with the elevated risk of diabetes in later life after adjusting for covariates (OR = 1.37; 95%CI: 1.09–1.72; P = 0.008). Stratified analysis showed that the association between prenatal famine exposure and diabetes risk in adulthood was comparable between severely affected areas and less severely affected areas (P for interaction =0.153). Conclusions Famine exposure in fetal stages was associated with the elevated diabetes risk in adults, which could be the critical periods for relative intervention.

Abstract Background Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) DNA has been demonstrated to be associated with obesity in the methylation level, and it also has a Body Mass Index (BMI)-independent association with plasma alanine aminotransferase (ALT). However, the relation among obesity, plasma ALT, HIF3A polymorphism and methylation remains unclear. This study aims to identify the association between HIF3A polymorphism and plasma ALT, and further to determine whether the effect of HIF3A polymorphism on ALT could be modified by obesity or mediated by DNA methylation. Methods The HIF3A rs3826795 polymorphism was genotyped in a case-control study including 2030 Chinese children aged 7–18 years (705 obese cases and 1325 non-obese controls). Furthermore, the HIF3A DNA methylation of the peripheral blood was measured in 110 severely obese children and 110 age- and gender- matched normal-weight controls. Results There was no overall association between the HIF3A rs3826795 polymorphism and ALT. A significant interaction between obesity and rs3826795 in relation with ALT was found (P inter = 0.042), with rs3826795 G-allele number elevating ALT significantly only in obese children (β’ = 0.075, P = 0.037), but not in non-obese children (β’ = −0.009, P = 0.741). Additionally, a mediation effect of HIF3A methylation was found in the association between the HIF3A rs3826795 polymorphism and ALT among obese children (β’ = 0.242, P = 0.014). Conclusion This is the first study to report the interaction between obesity and HIF3A gene in relation with ALT, and also to reveal a mediation effect among the HIF3A polymorphism, methylation and ALT. This study provides new evidence to the function of HIF3A gene, which would be helpful for future risk assessment and personalized treatment of liver diseases.

Recent studies indicated that eating behaviors are under genetic influence, and the melanocortin 4 receptor (MC4R) gene polymorphisms can affect the total energy intake and the consumption of fat, protein and carbohydrates. Our study aims at investigating the association of the MC4R polymorphism with appetite and food intake among Chinese children.A family-based association study was conducted among 151 Chinese trios whose offsprings were overweight/obese children aged 9-15 years. The rs12970134 near MC4R was genotyped, and the Children Eating Behavior Questionnaire (CEBQ) and a self-designed questionnaire measuring food intake were performed. The FBAT and PBAT software packages were used.The family-based association analysis showed that there was a significant association between rs12970134 and obesity (Z = 2.449, P = 0.014). After adjusting for age, gender and standardized BMI, rs12970134 was significantly associated with food responsiveness (FR) among children (β'b = 0.077, Pb = 0.028), and with satiety responsiveness (SR) in trios (P = -0.026). The polymorphism was associated with beverage intake (β'b = 0.331, Pb = 0.00016 in children; P = 0.043 in trios), but not significantly associated with vegetable, fruit or meat intake (P>0.050). We further found a significant mediation effect among the rs12970134, FR and beverage intake (b = 0.177, P = 0.047).Our study is the first to report that rs12970134 near MC4R was associated with appetite and beverage intake, and food responsiveness could mediate the effect of rs12970134 on beverage intake in overweight and obese Chinese children population. Further studies are needed to uncover the genetic basis for eating behaviors, which could lead to develop and implement effective interventional strategies early in life.

Gene polymorphisms associated so far with body mass index (BMI) can explain only 1.18-1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS) have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is associated with obesity and other obesity-related phenotypes in Chinese children. The subjects included 110 severe obese cases aged 7-17y and 110 normal-weight controls matched by age and gender for measurement of blood DNA methylation levels at the HIF3A gene locus using the Sequenom's MassARRAY system. We observed significantly higher methylation levels in obese children than in controls at positions 46801642 and 46801699 in HIF3A gene (P

Background: The patatin like phospholipase containing domain 3 gene (PNPLA3) rs738409 C > G polymorphism, one of the most important gene polymorphisms involved in hepatic steatosis, has been reported to interact with different nutrients and dietary patterns on Non-Alcoholic Fatty Liver Disease (NAFLD), but no studies have focused on its interaction with physical activity or sedentary behavior. Therefore, this study aims at determining whether physical activity or sedentary behavior could modulate the effect of the PNPLA3 variant on childhood NAFLD. Methods: A case-control study was conducted including 1027 Chinese children aged 7-18 years old (162 children with NAFLD and 865 children without). The anthropometric measurements, liver ultrasound examination, questionnaires and genotyping of the PNPLA3 rs738409 polymorphism were performed. Results: Stratified analyses showed that the proportions of NAFLD increased with the G-allele number only in children who did not have enough physical activity (physical activity < 1 h/d) (OR 3.05, 95% CI 1.82-5.12, P < 0.001), and in children with a sedentary lifestyle (sedentary behavior ⩾ 2 h/d) (OR 3.41, 95% CI 1.88-6.18, P < 0.001). Significant interactions on childhood NAFLD were found between the G-allele number in the PNPLA3 rs738409 polymorphism and behaviors, including physical activity (P = 0.001), sedentary behavior (P = 0.010) and the combination of physical activity and sedentary behavior (P < 0.001). Conclusion: This is the first study to report the interaction between the PNPLA3 rs738409 polymorphism and physical activity or sedentary behavior on NAFLD, providing new clues on the function of the PNPLA3 gene, which will also be useful for future risk assessment and personalized treatment of NAFLD. [ABSTRACT FROM AUTHOR]