Beijing Child And Adolescent Metabolic Syndrome Research Articles

1601-P: Childhood Plasma Amino Acid Profiles Predict the 10-Year Risk of Nonalcoholic Fatty Liver Disease—The BCAMS Study

Background and Aims: Amino acid profiles have been proved a promising tool to identify novel biomarkers and insight of the mechanisms of metabolic diseases; however, date on youth was still limited, particularly nonalcoholic fatty liver disease (NAFLD). We aimed to prospectively investigate if there exist any association between childhood plasma amino acid profiles and adulthood NAFLD, and explore the early predictor and the underlying mechanism for the development of hepatic steatosis. Methods: A total of 307 subjects aged 12.1±3.0 years at baseline were enrolled in this study at 10-year follow-up, recruited from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study cohort, including 99 NAFLD patients and 208 normal controls. Thirty-two amino acids (AAs) in fasting plasma at baseline were evaluated by liquid chromatograph-mass spectrometry. NAFLD was diagnosed by abdominal ultrasonography at follow-up. Results: Among the 32 qualified AAs, 14 AAs showed significant differences (p<0.05) between NAFLD and normal controls, including four AAs survived Bonferroni correction (p<0.0016). Adjustment for age, gender and lifestyle factors, there were 10 AAs remain significant, including alanine, asparagine, glutamine, glycine, isoleucine, tyrosine, serine and threonine etc. Further adjustment for BMI, lower levels of asparagine (OR: 0.62, 95% CI: 0.44-0.87), glutamine (OR: 0.73, 95% CI: 0.53-0.99) and serine (OR: 0.71, 95% CI: 0.51-0.98) remain significant predictors of NAFLD at the 10-year follow-up. Conclusion: Plasma amino acid profiles in childhood can predict risk of NAFLD in young adults. Plasma asparagine, glutamine and serine are likely to be early predictors of NAFLD independently of adiposity. Disclosure M.Li: None. S.Gao: None. Bcams group: n/a. Funding National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014); National Natural Science Foundation of China (81970732, 82270924); Capital's Funds for Health Improvement and Research (2020-2Z-40117); CAMS Innovation Fund for Medical Sciences (C

Puberty Status Modifies the Effects of Genetic Variants, Lifestyle Factors and Their Interactions on Adiponectin: The BCAMS Study.

BackgroundHypoadiponectinemia has been associated with various cardiometabolic disease states. Previous studies in adults have shown that adiponectin levels were regulated by specific genetic and behavioral or lifestyle factors. However, little is known about the influence of these factors on adiponectin levels in children, particularly as mitigated by pubertal development.MethodsWe performed a cross-sectional analysis of data from 3,402 children aged 6-18 years from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. Pubertal progress was classified as prepubertal, midpuberty, and postpuberty. Six relevant single nucleotide polymorphisms (SNPs) were selected from previous genome-wide association studies of adiponectin in East Asians. Individual SNPs and two weighted genetic predisposition scores, as well as their interactions with 14 lifestyle factors, were analyzed to investigate their influence on adiponectin levels across puberty. The effect of these factors on adiponectin was analyzed using general linear models adjusted for age, sex, and BMI.ResultsAfter adjustment for age, sex, and BMI, the associations between adiponectin levels and diet items, and diet score were significant at prepuberty or postpuberty, while the effect of exercise on adiponectin levels was more prominent at mid- and postpuberty. Walking to school was found to be associated with increased adiponectin levels throughout puberty. Meanwhile, the effect of WDR11-FGFR2-rs3943077 was stronger at midpuberty (P = 0.002), and ADIPOQ-rs6773957 was more effective at postpuberty (P = 0.005), while CDH13-rs4783244 showed the strongest association with adiponectin levels at all pubertal stages (all P < 3.24 × 10-15). We further found that effects of diet score (P interaction = 0.022) and exercise (P interaction = 0.049) were stronger in children with higher genetic risk of hypoadiponectinemia, while higher diet score and exercise frequency attenuated the differences in adiponectin levels among children with different genetic risks.ConclusionsOur study confirmed puberty modulates the associations between adiponectin, and genetic variants, lifestyle factors, and gene-by-lifestyle interactions. These findings provide new insight into puberty-specific lifestyle suggestions, especially in genetically susceptible individuals.

62-OR: Childhood Adipokine Profiles Predict the Incidence and Trajectory of Obesity in Young Adults: The BCAMS Study

Adipokine dysregulation is an early biomarker of adipose tissue dysfunction, which has been shown to relate to metabolic health. We aimed to investigate whether the profiles of certain adipokines in childhood might predict the incidence of obesity and contribute to BMI trajectory from childhood to young adulthood. A total of 3211 children aged 6-18ys from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study were evaluated at baseline, and 989 of these participants were assessed at 10-year follow-up. Physical activity, dietary and sleep information were collected by questionnaires. Baseline plasma adiponectin, leptin, resistin, retinol binding protein 4, osteonectin and fibroblast growth factor 21 (FGF-21) were measured by ELISA. The sex-adjusted z scores for adipokine levels were examined for their association with adiposity measures (BMI and waist circumference). Only 10.4% of the children who were non-obese at baseline developed obesity at 10-year follow-up, while over 65% of children presenting with obesity remained obese at follow-up, suggesting a well-established obesity trajectory over time. After adjusting for age, tanner stage, diet, exercise and sleep, decreased adiponectin and FGF-21 levels, as well as increased leptin, were associated with obesity risk both at baseline and 10-year follow-up (all P &amp;lt; 0.05). Multivariate analysis showed that after adjusting for confounding factors, each 1-SD increment in the leptin : adiponectin ratio was associated with a 3.26-fold (95% CI:2.08 - 5.10) higher risk for obesity at 10-year follow-up, while each 1-SD increment in FGF-21 level reduced the risk of obesity by 30% (95% CI: 0.48 - 0.96). Finally, among children with obesity at baseline, each 1-SD of elevation in resistin increased the risk of persistent obesity by 1.41-fold (95% CI: 1.13 - 1.77). These findings suggest that certain aberrant patterns of adipokine regulation during childhood may serve as biomarkers for the subsequent development of obesity. Disclosure S. Gao: None. M. Li: None. S.M. Willi: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Tolerion, Inc. Other Relationship; Self; Caladrius Biosciences, Inc. Funding National Natural Science Foundation of China (81970732); National Key Research Program of China (2016YFC1304801); Key Program of Beijing Municipal Science and Technology Commission (D111100000611001, D111100000611002); Beijing Natural Science Foundation (7172169); Beijing Science and Technology Star Program (2004A027), Novo Nordisk Union Diabetes Research Talent Fund (2011A002); National Key Program of Clinical Science (WBYZ2011-873); Central Research Institute Fund of Chinese Academy of Medical Sciences (2017PT32020, 2018PT32001); Beijing Chaoyang Hospital (JXPY201606)

Impact of parental smoking on adipokine profiles and cardiometabolic risk factors in Chinese children

Background and aimsThe mechanisms by which passive smoking leads to cardiometabolic risks, and the tissues involved still require elucidation. We aimed to evaluate the association of parental smoking exposure (PSE) with the secretion of adipocyte-derived hormones and cardiometabolic risk factors in Chinese children. MethodsWe included 3150 school children aged 6-18 years from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. Data on PSE and potential confounders were collected. Six adipokines related to insulin resistance and metabolic syndrome (MetS) were measured. ResultsPSE was reported in nearly two-thirds of the children. After adjusting for covariates, including age, sex, pubertal stages, lifestyle factors, and family history, PSE was independently associated with increases of 39.2% in leptin and 3.9% in retinol binding protein-4 and decreases of 11.4% in fibroblast growth factor 21 and 4.6% in adiponectin levels (p < 0.05 for all), plus risks for central obesity (OR 1.59, 95% CI 1.33–1.90), elevated blood pressure (1.22, 1.02–1.46) and MetS (1.43, 1.11–1.85). However, the associations of PSE with hypertension and MetS were abolished when adjusted for adiposity parameters or the above-mentioned adipokine profiles. ConclusionsPSE was associated with dysregulation of adipokine levels, which might mediate the development of MetS in early life.

Childhood sleep duration modifies the polygenic risk for obesity in youth through leptin pathway: the Beijing Child and Adolescent Metabolic Syndrome cohort study

Background/objectivesShort sleep is an obesity risk factor, however, little is known about its interplay with genetic predisposition and pathways involved in obesity pathogenesis, especially in the longitudinal setting. We aimed to investigate a possible sleep-gene interaction for childhood obesity risk, and whether the interaction in childhood longitudinally contributes to obesity risk at a 10-year follow-up and further to test if there is any mediation through the leptin pathway.Subjects/methodsA total of 3211 children from China (6–18 years) at baseline and 848 participants at 10-year follow-up from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) cohort study were analyzed. Baseline leptin concentrations and 12 established adult body mass index (BMI) loci were examined for the associations with habitual sleep duration.ResultsAfter adjusting for covariates, including pubertal stages and behavioral factors, short sleep duration at baseline was significantly associated with increased overweight/obesity risk at both baseline and follow-up. Genetic predisposition scores (GPS), particularly consisting of leptin-related SNPs (GPSleptin), were robustly associated with baseline overweight/obesity in children who slept ≤8 h/day (P < 0.001), whereas the association was ablated in those who slept ≥10 h/day (P > 0.05). Comparable observations were made at follow-up. Mediation analysis revealed a modest direct effect of the GPSleptin-sleep interaction on BMI at baseline, while a significant indirect effect of this interaction was found to be mediated principally through elevated leptin (proportion: 52.6%); moreover, the mediation effect via leptin remained stable over 10 years.ConclusionsThis study suggests that shorter sleep duration in children from China (< 8h/day), compared to longer sleep duration (≥10 h/day), has a long-term impact on the association of polygenic risk for obesity from childhood to young adulthood and leptin pathway explains a key mechanism via a modification effect. Therefore, adequate sleep duration during childhood is important for the early prevention of obesity, especially if there is a genetic predisposition to this trait.

Circulating Osteonectin and Adipokine Profiles in Relation to Metabolically Healthy Obesity in Chinese Children: Findings From BCAMS.

BackgroundThe role of adipokine dysregulation in determining the metabolic fate of obesity is not well studied. We aimed to examine whether the matricellular protein osteonectin and the profiles of certain adipokines could differentiate metabolically healthy obese (MHO) versus metabolically unhealthy obese phenotypes in childhood.Methods and ResultsThis study included 1137 obese children and 982 normal‐weight healthy (NWH) controls recruited from the BCAMS (Beijing Child and Adolescent Metabolic Syndrome) study. MHO was defined by the absence of insulin resistance and/or any metabolic syndrome components. Six adipokines—osteonectin, leptin, adiponectin, resistin, FGF21 (fibroblast growth factor 21), and RBP‐4 (retinol binding protein 4)—were assessed. Approximately 20% of obese children displayed the MHO phenotype. MHO children had a more favorable adipokine profile than metabolically unhealthy obese children, with lower osteonectin, leptin, and RBP‐4 and higher adiponectin (all P<0.05). Compared with normal‐weight healthy controls, MHO children displayed increased leptin, resistin, and RBP‐4 levels and reduced adiponectin concentrations (all P<0.05) but similar osteonectin and FGF21 levels. Among obese subjects, decreased osteonectin (odds ratio [OR]: 0.82; 95% confidence interval [CI] per standard deviation, 0.70–0.97), RBP‐4 (OR: 0.77; 95% CI per standard deviation, 0.64–0.93), and leptin/adiponectin ratio (OR: 0.58; 95% CI per standard deviation, 0.43–0.77) were independent predictors of MHO. In addition, compared with children without abnormalities, those with any 3 adipokine abnormalities were 80% less likely to exhibit the MHO phenotype (OR: 0.20; 95% CI, 0.10–0.43) and 3 times more likely to have metabolic syndrome (OR: 2.77; 95% CI, 1.52–5.03).ConclusionsThese findings suggest that dysregulation of adipokines might govern the metabolic consequences of obesity in children. Low osteonectin levels, along with a healthy adipokine profile, might be used as an early marker of the MHO phenotype.

Childhood Habitual Sleep Duration Modifies the Polygenic Risk for Obesity through Leptin Pathway—A Longitudinal Study

Sleep disruption is known to be an obesity risk factor, however, little is known about its interplay with genetic predisposition and pathways involved in obesity pathogenesis, especially in the longitudinal setting. Leveraging a large cohort from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study, we aimed to examine a possible sleep-gene interaction for childhood obesity risk, including longitudinal assessment in a 10-year follow-up and further test if there is any mediation through the leptin pathway. A total of 3,211 children (6-18 years) were recruited from this cohort study. Baseline leptin levels and twelve established adult BMI loci were examined for the associations with habitual sleep duration. After adjusting for pubertal stages, diet score and activity, short sleep duration at baseline was significantly associated with increased overweight/obesity risk at both baseline and follow-up. Genetic predisposition scores, particularly consisting of the central nervous system (CNS) gene variation (GPSCNS), were robustly correlated with baseline overweight/obesity in children who slept ≤8h/day (P&amp;lt;0.001), whereas the association was ablated in those who slept ≥10h/day (P&amp;gt;0.05). Comparable observations were made at follow-up. Mediation analysis revealed a modest direct effect of the GPSCNS-sleep interaction on BMI at baseline, while an indirect effect of this interaction was found to be mediated principally through elevated leptin (52.6%); moreover, the mediation effect via leptin remained stable over 10 years. This study provides longitudinal evidence that short sleep duration in children has a long-term impact on the association of polygenic risk for obesity from childhood to young adulthood and leptin pathway explains a key mechanism via a modification effect. Therefore, adequate sleep duration during childhood is important for the early prevention of obesity, especially if there is a genetic predisposition to this trait. Disclosure M. Li: None. J. Fu: None. L. Han: None. G. Li: None. S. Gao: None. S.F. Grant: None.

Associations of the hypertension-related single nucleotide polymorphism rs11191548 with high-density lipoprotein cholesterol and leptin in Chinese children

BackgroundThe genome-wide association study has founded hypertension-related single nucleotide polymorphism (SNP) rs11191548 near CYP17A1 encoding a key enzyme involved in steroid metabolism, but the molecular mechanisms are not understood and the associations of the SNP with hypertension-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNP and two hypertension-related traits, lipids and leptin.MethodsWe genotyped the SNP in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study.ResultsThe SNP rs11191548 was significantly associated with high-density lipoprotein cholesterol (HDL) (P = 0.014 and 0.028, respectively) and leptin (P = 0.011 and 0.026, respectively) under an additive model after adjustment for age, gender, and systolic blood pressure (SBP) or diastolic blood pressure (DBP). There was a statistically significant association of rs11191548 with high leptin after adjustment for age, gender, and SBP or DBP. The P-values remain significant after correction for multiple testing.ConclusionsWe demonstrate for the first time that the SNP rs11191548 near CYP17A1 is associated with HDL and leptin in Chinese children. These novel findings provide important evidence that HDL and leptin maybe possibly mediate the process of CYP17A1 involved in hypertension.

Association between rs10938397 polymorphism in GNPDA2 and obesity in children at different stages of development

Objective: To examine the association between rs10938397 polymorphism in glucosamine-6-phosphate deaminase 2 (GNPDA2) and risk of obesity in children at different stages of development and analyze the differences in the association. Methods: A total of 3 503 school-aged children were selected from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study in Beijing and their complete anthropometry weight, height, fat mass percentage (FMP), fat mass index (FMI) and free fat mass index (FFMI) and sexual maturation (SM) data were used. The developmental stages were evaluated using male testicular volume and female breast Tanner staging. FMP, FM and FFM were measured by bioelectrical impedance analysis. General obesity and adiposity were respectively defined according to Chinese sex-age-specific body mass index (BMI) cutoffs and sex-age-specific FMP cutoffs. The SNP rs10938397 were genotyped by the TaqMan Allelic Discrimination Assay with the GeneAmp 7900 sequence detection system (Applied Biosystems, Foster city, CA, USA). Relationships between rs10938397 polymorphism and BMI, FMP, FMI and FFMI and different types of obesity were tested using multivariate linear regression and logistic regression models. Results: After age adjustment and correction for multiple testing, the rs10938397-G was associated with BMI and risk of general obesity in boys in early puberty (β=0.328, P=0.001; OR=1.420, 95%CI: 1.126-1.790), and the rs10938397-G was associated with BMI in girls in late puberty (β=0.266, P=0.001). The associations of GNPDA2 rs10938397-G with FFMI and FMI were observed in boys in early puberty (β=0.137, P=0.016; β=0.202, P=0.007) and the associations of rs10938397-G with FMP and FMI were observed in girls in late puberty (β=0.153, P=0.002; β=0.168, P=0.001). The rs10938397-G was also associated with adiposity in girls in late puberty (OR=1.339, 95%CI: 1.093-1.637). Conclusion: The rs10938397 polymorphism in GNPDA2 is associated with adiposity in girls, and it is important to use an accurate indicator of obesity in exposing the genuine association between genes and obesity.

Adipokines are Associated With Hypertension in Metabolically Healthy Obese (MHO) Children and Adolescents: A Prospective Population-Based Cohort Study.

BackgroundThe potential mechanism underlying the relationship between the risk of cardiovascular diseases and metabolically healthy obese (MHO) individuals remains unclear. The aim of the study was to prospectively investigate the potential role of the adipokines in the association between the MHO phenotype and hypertension in children and adolescents.MethodsA total of 1184 participants at baseline were recruited from a cohort of the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. The participants were classified according to their body mass index (BMI) and metabolic syndrome (MS) components. The levels of the adipokines, including leptin, adiponectin, and resistin, were measured.ResultsMHO individuals had higher leptin levels (11.58 ug/L vs 1.20 ug/L), leptin/adiponectin ratio (1.18 vs 0.07), and lower adiponectin (11.65 ug/L vs 15.64 ug/L) levels compared to metabolically healthy normal-weight individuals (all P < 0.05). Compared to metabolically healthy normal-weight individuals, the prevalence of high leptin levels (26.5% vs 0.4%), low adiponectin levels (17.9% vs 6.3%) and a high leptin/adiponectin ratio (26.0% vs 2.1%) was higher in MHO individuals (all P < 0.01). The MHO individuals with abnormal adipokines were significantly more likely to developing hypertension (high leptin, relative risk 11.04; 95% confidence interval, 1.18–103.35; and high leptin/adiponectin ratio, relative risk 9.88; 95% confidence interval, 1.11–87.97) compared to metabolically healthy normal-weight individuals with normal adipokine levels.ConclusionsThe abnormal adipokine levels contribute to the increased hypertension risk in MHO children and adolescents. The non-traditional risk factors should be highlighted in MHO children and adolescents in clinical practice and research.

Gene-gene interaction on central obesity in school-aged children in China

Objective: To investigate possible effect of 6 obesity-associated SNPs in contribution to central obesity and examine whether there is an interaction in the 6 SNPs in the cause of central obesity in school-aged children in China. Methods: A total of 3 502 school-aged children who were included in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study were selected, and based on the age and sex specific waist circumference (WC) standards in the BCAMS study, 1 196 central obese cases and 2 306 controls were identified. Genomic DNA was extracted from peripheral blood white cells using the salt fractionation method. A total of 6 single nucleotide polymorphisms (FTO rs9939609, MC4R rs17782313, BDNF rs6265, PCSK1 rs6235, SH2B1 rs4788102, and CSK rs1378942) were genotyped by TaqMan allelic discrimination assays with the GeneAmp 7900 sequence detection system (Applied Biosystems, Foster City, CA, USA). Logistic regression model was used to investigate the association between 6 SNPs and central obesity. Gene-gene interactions among 6 polymorphic loci were analyzed by using the Generalized Multifactor Dimensionality Reduction (GMDR) method, and then logistic regression model was constructed to confirm the best combination of loci identified in the GMDR. Results: After adjusting gender, age, Tanner stage, physical activity and family history of obesity, the FTO rs9939609-A, MC4R rs17782313-C and BDNF rs6265-G alleles were associated with central obesity under additive genetic model (OR=1.24, 95%CI: 1.06-1.45, P=0.008; OR=1.26, 95%CI: 1.11-1.43, P=2.98×10(-4); OR=1.18, 95% CI: 1.06-1.32, P=0.003). GMDR analysis showed a significant gene-gene interaction between MC4R rs17782313 and BDNF rs6265 (P=0.001). The best two-locus combination showed the cross-validation consistency of 10/10 and testing accuracy of 0.539. This interaction showed the maximum consistency and minimum prediction error among all gene-gene interaction models evaluated. Moreover, the combination of MC4R rs17782313-C and BDNF rs6265-G was associated with an increased risk of central obesity after adjustment for gender, age, Tanner stage, physical activity and family history of obesity. Conclusions: Our study showed that FTO rs9939609-A, MC4R rs17782313-C and BDNF rs6265-G alleles were associated with central obesity, and statistical interaction between MC4R rs17782313-C and BDNF rs6265-G increased risk of central obesity in school-aged children in China.

Associations of Two Obesity-Related Single-Nucleotide Polymorphisms with Adiponectin in Chinese Children.

Purpose. Genome-wide association studies have found two obesity-related single-nucleotide polymorphisms (SNPs), rs17782313 near the melanocortin-4 receptor (MC4R) gene and rs6265 near the brain-derived neurotrophic factor (BDNF) gene, but the associations of both SNPs with other obesity-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNPs and adiponectin that has a regulatory role in glucose and lipid metabolism. Methods. We examined the associations of the SNPs with adiponectin in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study. Results. The SNP rs6265 was significantly associated with adiponectin under an additive model (P = 0.02 and 0.024, resp.) after adjustment for age, gender, and BMI or obesity statuses. The SNP rs17782313 was significantly associated with low adiponectin under a recessive model. No statistical significance was found between the two SNPs and low adiponectin after correction for multiple testing. Conclusion. We demonstrate for the first time that the SNP rs17782313 near MC4R and the SNP rs6265 near BDNF are associated with adiponectin in Chinese children. These novel findings provide important evidence that adiponectin possibly mediates MC4R and BDNF involved in obesity.

LBPS 01-07 STUDY OF 6 BMI-ASSOCIATED LOCI IDENTIFIED IN GWAS FOR INTERACTIVE ASSOCIATIONS WITH CENTRAL OBESITY IN THE CHINESE CHILDREN

Objective: Recent genome-wide association studies have identified many single nucleotide polymorphisms (SNPs) associated with body mass index (BMI)/generalized obesity. In this study, we aimed to evaluate the interactive associations of identified SNPs with risk of central obesity in a child population from China. Design and Method: We genotyped 6 SNPs (FTO rs9939609, MC4R rs17782313, BDNF rs6265, PCSK1 rs6235, SH2B1 rs4788102, CSK rs1378942) in the Chinese children (N = 3502, age range 6–18 years) from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS). Based on the age- and sex- specific waist circumference (WC) standards generated in the BCAMS study, 1196 central obese cases and 2306 controls were identified. We analyzed gene-gene interactions among 6 polymorphic loci using the Generalized Multifactor Dimensionality Reduction (GMDR) method, and then used logistic regression models to confirm the best combination of loci identified in the GMDR. Results: GMDR analysis showed a significant gene-gene interaction between the rs17782313 polymorphism in the MC4R gene and the rs6265 polymorphism in the gene BDNF. The best two-locus combination scored 10 for cross-validation consistency and 10 for sign test (P = 0.0010). This interaction showed the maximum consistency and minimum prediction error among all gene-gene interaction models evaluated. Moreover, the combination of the MC4R rs17782313 and the BDNF rs6265 was associated with a significantly increased risk of central obesity (OR = 1.48, 95% CI:1.25–1.74; P = 3.70 × 10–6) after adjustment for sex, age, pubertal stage, physical activity and family history of obesity. Conclusions: Our study showed the statistically interactive association between the MC4R rs17782313 and the BDNF rs6265 with risk of central obesity in the Chinese children, revealing that these genes affect obesity more likely through a complex interaction pattern than single gene effect.

Risk of obesity-related gene polymorphism on the incidence and durative of childhood obesity

To examine the impact of single nucleotide polymorphisms(SNPs)in obesity-related genes on the incidence and durative of obesity in childhood and adolescence. Based on the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study, 780 school children aged 6 to 16 years were followed-up in 2010, and assessed for body size parameters. Venipuncture blood samples were collected after a 12-hour overnight fast. Genomic DNA was isolated from peripheral blood white cells under the salt fractionation method. SNPs were genotyped by ABI 5700 real time PCR(FTO rs9939609)and TaqMan Allelic Discrimination Assays with the GeneAmp 7900 Sequence Detection System(Applied Biosystems,Foster City, CA, USA) (FTO rs6499640, FAIM2 rs7138803,NPC1 rs1805081, MC4R rs17782313, BDNF rs6265, GNPDA2 rs10938397). Both overweight and obesity were diagnosed by the Chinese age- and sex- specific body mass index(BMI) cutoffs. Two independent sample t-test, Chi-square test and multiple logistic regression analysis were performed. During the 6 years follow-up period, the incidence of obesity in the total sample 8.5%, and 65.1% individuals had persisted their obese status. The genotypes of the SNPs except BDNF rs6265 were in Hardy-Weinberg equilibrium in each group (P > 0.05). The incidence rates of obesity increased with FTO rs9939609 TT,TA and AA genotypes(χ(2) for trend = 8.030, P < 0.05). In the non-obese sub-cohort, after adjusted for sex, age at the initial time of follow up and residential area, when compared with children carrying FTO rs9939609 T-allele, a significantly relative risk of obesity was observed for children carrying the rs9939609 A-allele(OR = 2.42, 95%CI:1.31-4.47, P = 0.005). In the obese sub-cohort, FTO rs9939609 A-allele was significantly associated with durative of obesity (OR = 1.72, 95%CI:1.07-2.77, P = 0.026). However, no statistical significant associations were seen between other SNPs(FTO rs6499640, FAIM2 rs7138803, NPC1 rs1805081, MC4R rs17782313, GNPDA2 rs10938397)and the incidence or durative of obesity(all P > 0.05). The genetic risk score was associated with the risk of occurrence of obesity(OR = 16.42, 95% CI:3.59-75.10, P < 0.001) after adjusted for residential area, sex, age at the initial time of follow up and baseline BMI. We confirmed the association of FTO rs9939609 with incidence and durative of obesity in children. Early intervention was recommended on the high risk individuals who carrying more risk alleles in obesity-related genes.

Study of 11 BMI-Associated Loci Identified in GWAS for Associations with Central Obesity in the Chinese Children

ObjectiveRecent genome-wide association studies have identified many single nucleotide polymorphisms (SNPs) associated with body mass index (BMI)/generalized obesity. In this study, we aimed to examine the associations of identified SNPs with risk of central obesity in a child population from China.MethodsWe genotyped 11 SNPs (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397, BDNF rs6265, FAIM2 rs7138803, NPC1 rs1805081, SEC16B rs10913469, SH2B1 rs4788102, PCSK1rs6235, KCTD15 rs29941, BAT2 rs2844479) in the Chinese children (N = 3502, age range 6–18 years) from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS). Based on the age- and sex- specific waist circumference (WC) standards generated in the BCAMS study, 1196 central obese cases and 2306 controls were identified.ResultsOf 11 studied SNPs, four SNPs and genetic risk score (GRS) based on them were statistically significantly associated with central obesity by WC criteria (FTO rs9939609: OR = 1.29, 95%CI = 1.10–1.50, p = 0.001; MC4R rs17782313: OR = 1.27, 95%CI = 1.12–1.44, p = 1.32×10−4; GNPDA2 rs10938397: OR = 1.22, 95%CI = 1.09–1.37, p = 4.09×10−4; BDNF rs6265: OR = 1.20, 95%CI = 1.08–1.34, p = 8.86×10−4; GRS: OR = 1.25, 95%CI 1.16–1.34, p = 2.58×10−9) after adjustment for sex, age, pubertal stage, physical activity and family history of obesity. Similar observations were made using weight-to-height ratio (WHtR) criterion. However, other SNPs were not associated with central obesity by WC as well as WHtR criterion.ConclusionsOur study replicates the statistically significant association of four SNPs (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397, BDNF rs6265) with risk of central obesity in the Chinese children.

Association between obesity in childhood and hypertension incidence: A prospective cohort study

Objective: To explore the association between obese level as well as the level of change in childhood and hypertension incidence. Methods: A perspective cohort study was conducted. As part of Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study, 2189 non-hypertensive children aged 6–16years at school were followed up in 2010. In this study, height, weight, waist circumference (WC) and blood pressure was measured at follow-up, and body mass index (BMI) and WC was respectively used to assess overweight/obesity and abdominal obesity.

Impact of insulin resistance and obesity on elevated blood pressure in Chinese children and adolescents: The BCAMS study

Objective: Insulin resistance (IR) in the obese is closely related with cardiovascular diseases and their risk factors not only in adults but also in children and adolescents. We aimed to elucidate whether insulin resistance in non-obese children and adolescents is related with elevated blood pressure (BP). Methods: Subjects were recruited from a cross-sectional population-based survey: the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. The present sample of 3480 students (1774 boys, 51%) was drawn from children aged 6 to 18 years who underwent physical examinations and fasted before blood testing. Obese was defined by age and gender-specific body mass index cutoffs of China. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as fasting insulin (mU/L)×fasting glucose (mmol/L)/22.5. HOMA-IR levels above the highest quartile (>3.09 for boys and >2.83 for girls) were defined as IR. Participants were divided as four groups, i.e. normal group (non-obese and no IR, n=1923), IR group (non-obese but IR, n=338), obese group (obese but no IR, n=684) and obese combined IR group (n=535). Elevated BP was defined by systolic BP and/or diastolic BP equal to or greater than the 95th percentile for age and gender. Results: In obese combined IR groups, both systolic and diastolic BP levels were highest, followed by the obese, IR and normal groups (P<0.001 for trend) with age, gender and puberty adjusted. Prevalence of elevated BP was 8.2%, 16.1%, 29.2% and 38.3% in normal, IR, obese and obese combined IR groups, respectively (χ2=335.627, P<0.001 for trend). Adjusting for age, gender and puberty, compared with normal group, odds ratios and 95% confidence intervals of IR, obese and obese combined IR on elevated BP were 2.10 (1.50–2.96), 4.54 (3.56–5.80) and 6.21 (4.84–7.96), respectively. Conclusion: IR independently increases the risk of elevated BP not only in obese but also in non-obese children and adolescents.

Impact on the risk of obesity due to interactions between fat mass- and obesity-associated gene rs9939609 variants and behavioral factors, in the Chinese school-aged children

To investigate how the interactions between fat mass- and obesity-associated (FTO) gene rs9939609 variants and daily-life related behavioral factors would influence the risk of obesity among the Chinese school-aged children. 3503 school-aged children were selected from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study, and divided into obese children (n = 1229) and non-obese children (n = 2274). Venipuncture blood test, genotyping and questionnaire were performed. Five common factors including protein foods, tobacco & alcohol, vegetables & fruits, sedentary behavior and physical exercise in spare time were extracted with factor analysis methodology. Data from logistic regression analysis showed that taking the interaction of rs9939609 variant with protein foods as an example, the risk of interaction accounted for 19.16% when both factors existing simultaneously. Similarly, the interactions of this SNP with vegetables & fruits, sedentary behavior and physical exercise in spare time appeared to be 5.97%, 19.62% and 12.43% respectively; however there might not be interaction between tobacco, alcohol and the SNP in the Chinese children. Protein foods, vegetables & fruits, sedentary behavior and physical exercise might modify the effects of FTO rs9939609 variant on the risk of obesity in Chinese school-aged children. However, large-scale, prospective studies with detailed information on related behavioral factors would be ideal models for identifying the interactions between genes and environment.