FTO and MC4R polymorphisms, and selected pre-, peri- and postnatal factors as determinants of body mass index and fatness in children: a thorough analysis of the associations.

BACKGROUND: Overweight and obesity among children have become significant global health concerns. Previous studies have highlighted the potential role of genetic factors, particularly polymorphisms in the FTO and MC4R genes, as well as environmental factors in the development of childhood obesity. This study aimed to investigate the relationships between genetic, socioeconomic and perinatal factors, adverse childhood events (ACEs), and lifestyle, and their impact on overweight, obesity and body composition parameters in children. Additionally, we explored potential interactions between genetic factors and ACEs. METHODS: Four hundred fifty-six children aged 6-12 years participated in our study. Information on the socioeconomic status, perinatal factors, ACEs and lifestyle of the children was collected with a questionnaire completed by their parents/guardians. We examined the children's body weight and conducted an electrical bioimpedance analysis. Overweight and obesity were diagnosed based on the International Obesity Task Force and McCarthy criteria. We genotyped two selected polymorphisms in the FTO and MC4R genes using the TaqMan SNP allelic discrimination method. RESULTS: Higher BMI (Body Mass Index) z scores were related to higher paternal BMI and lower maternal age at the child's birth. Higher FMI (Fat Mass Index) z scores were associated with higher paternal BMI, increased gestational weight, lower maternal education and the presence of the FTO risk allele. Higher FatM (fat mass in kg) z scores were linked to lower maternal education, lower maternal age at the child's birth, higher maternal body weight gain, paternal BMI and the presence of the FTO risk allele. Moreover, interaction effects were observed on BMI z scores between ACE and FTO AA, and on FMI z scores and FatM z scored between ACE and MC4R CC. CONCLUSIONS: The contribution of environmental factors is more strongly related to changes in body composition than genetic ones. Additionally, the presence of the risk allele combined with unfavourable environmental factors like ACEs leads to visible interaction effects, resulting in increased BMI z scores and FMI z scores in children.

Cool executive functions and their association with body mass & fatness and the FTO gene in school-aged children.

The FTO gene rs9936909 polymorphism is one of the well-documented single nucleotide polymorphisms in the context of increased risk of obesity, including in children. Few studies have tested the association of the FTO gene with cognitive functions. Deficits of "cool" executive functions (EFs) are considered a potential risk factor for excessive weight. The aims of our study were to investigate whether cool EFs are associated with the Body Mass Index, the Fat Mass Index and the risk of excess body mass and overfatness in neurotypically school-aged children, and whether the FTO gene polymorphism is involved in development of this possible association. The sample consisted of 553 children aged 6-12 years old. A body composition analysis, a neuropsychological assessment of EFs, and FTO polymorphism genotyping were performed in the children studied. The study found a significant association of an interference effect in theStroop Color-Word Interference Task and the risk of excessive body fatness, but not excessive body mass. There were no explicit associations between the FTO genotype and EFs deficits. Environmental factors, and particularly low maternal education, appeared to be the strongest contributors to the increased risk of obesity.

The relation between prenatal stress, overweight and obesity in children diagnosed according to BMI and percentage fat tissue.

BACKGROUND: One of the environmental factors contributing to abnormal weight changes in children may be maternal exposure to adverse environmental factors during pregnancy, which in previous studies led to inconclusive results showing both overweight or obesity and underweight in children. The aim of the study was to assess the influence of prenatal stress on the BMI status and cut-off points for the percentage of fat content. METHODS: The cohort study included 254 girls and 276 boys. Information on prenatal stress was collected retrospectively with a questionnaire on objective adverse events completed by a parent/guardian of a 6-12-year-old child. We examined the body weight of children and performed an electrical bioimpedance analysis of their body composition. We assessed the BMI status according to the International Obesity Task Force (IOTF) criterion and on the basis of body fat according to McCarthy criterion. RESULTS: The results of our study show that the prenatal stress was related to increased risk of overweight (OR 2.14, 95% CI: 1.25-3.65) diagnosed on the basis of body fat cut-off points, but not when the BMI was a diagnostic criterion (OR 1.03, 95% CI: 0.58-1.83). CONCLUSION: The method of diagnosis based on the fat content appears to be an indicator of the occurrence of abnormalities in body composition due to prenatal stress more sensitive than that based on the BMI. LEVEL OF EVIDENCE: Level III evidence obtained from well-designed cohort or case-control analytic studies.

Association of adverse childhood experiences (ACEs) with obesity and underweight in children.

PURPOSE: The aim of the study was to test the hypothesis that adverse childhood experiences (ACEs) are related to both obesity and underweight from childhood, and that the association of ACEs with weight abnormalities is modulated by type of ACEs, sex and socioeconomic status (SES) indices. METHODS: The relations between ACEs (0 vs ≥ 1), ACE accumulation and ACE type with weight status and z scores BMI were assessed in 503 children aged 6-12 years from Poznan, Poland. The effects of interaction of ACEs with sex and SES on z scores BMI were included in the analyses. RESULTS: ACEs were significantly related to both obesity and underweight, in unadjusted analysis, and when sex and SES indices, such as size of place of residence, people per room in household, and parental education were controlled. The relation of ACEs with z scores BMI was modulated by ACE type, parental subjective assessment of economic situation of a family and parental education. ACE accumulation was not related to an increase of obesity or underweight rate, or z scores BMI. CONCLUSION: The study implicates the need for both obesity and underweight prevention in individuals with adverse experiences as early as in childhood. LEVEL OF EVIDENCE: III: evidence obtained from well-designed cohort study.

Common and Unique Genetic Background between Attention-Deficit/Hyperactivity Disorder and Excessive Body Weight.

Comorbidity studies show that children with ADHD have a higher risk of being overweight and obese than healthy children. This study aimed to assess the genetic alternations that differ between and are shared by ADHD and excessive body weight (EBW). The sample consisted of 743 Polish children aged between 6 and 17 years. We analyzed a unique set of genes and polymorphisms selected for ADHD and/or obesity based on gene prioritization tools. Polymorphisms in the KCNIP1, SLC1A3, MTHFR, ADRA2A, and SLC6A2 genes proved to be associated with the risk of ADHD in the studied population. The COMT gene polymorphism was one that specifically increased the risk of EBW in the ADHD group. Using the whole-exome sequencing technique, we have shown that the ADHD group contains rare and protein-truncating variants in the FBXL17, DBH, MTHFR, PCDH7, RSPH3, SPTBN1, and TNRC6C genes. In turn, variants in the ADRA2A, DYNC1H1, MAP1A, SEMA6D, and ZNF536 genes were specific for ADHD with EBW. In this way, we confirmed, at the molecular level, the existence of genes specifically predisposing to EBW in ADHD patients, which are associated with the biological pathways involved in the regulation of the reward system, intestinal microbiome, and muscle metabolism.

Do Hot Executive Functions Relate to BMI and Body Composition in School Age Children?

Deficits of 'hot' executive functions (EFs) involving emotional and motivational processes are considered as a risk factor for excessive weight, but few studies have tested the relationship between hot EFs and body composition in children. The aim of the study was to assess the association of the ability to delay gratification and affective decision-making with the body mass index (BMI) and body composition in children with typical neurocognitive development. The sample consisted of 553 Polish children aged between 6-12 y. The delay of gratification task (DGT) was applied to assess the ability to delay gratification. The Hungry Donkey test (HDT) was applied to assess affective decision-making. The indicators of decision-making in the HDT were net score and learning rate. The relationships between hot EFs and BMI, fat mass index (FMI), lean body mass index (LBMI) were tested. The association of the z scores of BMI and FMI, overweight/obesity, and the ability to delay gratification was found insignificant after controlling cofounding factors. Most of the results on affective decision-making and z scores for BMI, FMI and LBMI were insignificant as well. The relationship between the ability to delay gratification, affective decision-making, and adiposity is not pronounced in typically developed children.

Stress/Immune Biomarkers in Saliva among Children with ADHD Status.

Background. This cross-sectional study aimed to evaluate stress and immune biomarkers in saliva samples of attention-deficit/hyperactivity disorder ADHD compared to healthy non-ADHD children. Material and methods. A total of 132 children under 11 years old (8.5 ± 1.1) enrolled in a cross-sectional study: with confirmed ADHD (n = 60) and healthy controls (n = 72). The clinical evaluation included physical measurements (height, waist, hip circumference, body weight, body mass index BMI, BMI z-score) and unstimulated saliva collection and measurements of free cortisol, salivary alpha-amylase (sAA), and secreted immunoglobulins (sIgA, IgG, and IgM) with quantitative assay (ELISA) analysis. Unpaired t-test, Welch test, or Mann-Whitney U test were applied for group comparisons when appropriate, and the correlation between variables was analyzed with Spearman's rank coefficient. Results were considered significant at p < 0.05. Results. In the ADHD group, body weight (p ≤ 0.01), BMI (p ≤ 0.009), and hip circumference (p ≤ 0.001) significantly differed, while waist size and BMI z-score did not (p > 0.05). Significant elevation of the salivary sAA (p = 0.03), sIgA (p = 0.02), and IgM (p ≤ 0.001) biomarkers were detected, without differences in the morning cortisol (p > 0.05). Significant correlations between cortisol and BMI, hip size, and IgA, as well as between IgG and sAA and IgA were obtained. Conclusions. Saliva can be used to monitor ADHD status with regard to biomarkers indicating the hypothalamus-pituitary-adrenal axis, as HPA axis, and sympathetic activity. The results indicate that morning collection of saliva in contrast to unchanged salivary cortisol, may evaluate mentioned above system dysregulations by measurements of sAA and immunoglobulins among ADHD children.

Salivary Biomarkers (Opiorphin, Cortisol, Amylase, and IgA) Related to Age, Sex, and Stress Perception in a Prospective Cohort of Healthy Schoolchildren.

BACKGROUND: The use of easily accessible biomarkers for assessing young patients' health is weighty. This cohort study is aimed at measuring stress/immune biomarkers in the saliva of healthy school-age children and comparing subgroups according to age, sex, and stress perception. Material and Methods. 503 children under 12 years old (8.7 ± 1.3) were included with anthropometric evaluation (height, waist, hip circumference, body weight, and body mass index (BMI)). Levels of opiorphin (OPI), free cortisol, alpha-amylase (sAA), and secreted immunoglobulin (sIgA) were determined by quantitative assays (ELISA) in unstimulated saliva. Unpaired t-test, Welch test, and Mann-Whitney U test were applied for appropriate group comparisons, and the correlation between variables was analyzed with Spearman's rank coefficient. Results were considered significant at p < 0.05. RESULTS: sIgA and sAA exhibited significant differences depending on age and sex: IgA (ng/mL): 86 ± 68.6 vs. 104.9 ± 72.1 for (6-7 y.o.) and (8-11 y.o.), respectively, and 108.1 ± 80.1 vs. 94.6 ± 62.2 for male and females, respectively; sAA (U/mL): 78.9 ± 54.4 vs. 100.5 ± 81.2 for (6-7 y.o.) and (8-11 y.o.). No difference related to age or sex between groups was observed for cortisol and OPI. However, OPI levels were higher and correlated to prior stress exposure in children (0.31 ± 0.4 vs. 0.26 ± 0.5 ng/mL, p = 0.031). sAA was negatively correlated to low mood self-declaration in children in the last two weeks (r = -0.10, p = 0.045). CONCLUSIONS: sIgA and sAA can be used as sex- and age-related biomarkers in children 6-12 y.o., which is not the case for free cortisol and opiorphin. However, OPI reflected previous exposure to stress, suggesting its use for evaluating stress-related changes in children.