Objective:To study the relationship between rs 2228314 polymorphism in sterol regulatory element binding protein 2 gene (SREBP2) and obesity, serum lipid levels in children and adolescents . Methods:In our study , 2 030 children and adolescents aged from 7 to 18 years participated .Anthropo-metric measurements, including height and weight, were performed.Their serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol ( HDL-C) were detected .The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS ) was used to detect rs2228314 genotypes.Results: The GC/CC genotypes of rs2228314 polymorphisms had lower HDL-C levels than GG genotype [(0.10 ±0.35) mmol/L vs. (0.14 ±0.36) mmol/L, P=0.020].The rs2228314 polymorphism was associated with the abnormal HDL-C level under the dominant model after adjustment for study samples , sex and age ( OR=1.400, 95%CI:1.027-1.907, P=0.033).The rs2228314 polymorphism was not associated with obesity un-der the dominant model after adjustment for study samples , sex, age and HDL-C level ( OR=1.178, 95%CI: 0 .971 -1 .430 , P =0 .096 ) . Conclusion: The GC/CC genotype carriers of SREBP2 rs2228314 polymorphism have higher risk of abnormal HDL-C level than the individuals with GG geno-type among children and adolescents .

Objective: To study the relationship between rs1136410 polymorphism in poly (ADP-ribose) polymerase-1 gene (PARP-1) with obesity and non-alcoholic fatty liver disease (NAFLD) in children and adolescents, and to provide a reference for demonstrating the mechanism of obesity and NAFLD of children and adolescents and making the early prevention strategies. Methods: In total, 2 030 children and adolescents aged 7-18 years old were recruited. Anthropometric measurements were performed. Liver B-ultrasound detection were performed in a subgroup. The matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TDF MS) was used for genotyping the rs1136410 polymorphism. Logistic regression was used to analyze the relationship between rs1136410 polymorphism and obesity or NAFLD in children and adolescents. Results: Totally, 1 325 subjects were in non-obese group and 705 subjects were in obese group. The frequency of G allele and A allele were 43.86% and 56.14%. After adjusting for gender, age, and study population, the risk of obesity increased by 1.17 times for each additional A allele of rs1136410 polymorphism(OR=1.17, 95%CI=1.02-1.33, P=0.03). And the risk of NAFLD increased by 1.43 times for each additional A allele of rs1136410 polymorphism(OR=1.43, 95%CI=1.11-1.85, P=0.01). After further adjustment for BMI, rs1136410 polymorphism was not associated with NAFLD(P=0.70). Conclusion The rs1136410 polymorphism in PARP-1 gene is associated with obesity and NAFLD in children and adolescents. The effect of the gene polymorphism on NAFLD is mediated by BMI.

Objective: To study the associations of rs 7498665 polymorphism located in the SH2B adaptor protein 1 gene with obesity related phenotypes in Chinese children and adolescents, and to explore the gene lifestyles interactions. Methods: Anthropometric measurements and lifestyles investigation were conducted in 3 305 children and adolescents aged 7-18 years old recruited from Beijing. The matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI TOF MS) was used to genotype rs 7498665 polymorphism. Multiple Logistic and linear regressions were performed to analyze the associations of rs 7498665 with obesity and obesity related phenotypes by different levels of physical activity and diet behavior. Results: The G allele of rs 7498665 polymorphism showed 37%, 101%, 45% and 64% high risk of obesity in population groups with unhealthy dietary intake, not eating breakfast daily, high consumption of sugar sweetened beverages or not daily moderate to vigorous physical activity ( P <0.05). In the further analysis, the G allele of rs 7498665 polymorphism was associated with obesity in population with unhealthy lifestyle score ( OR=1.63, 95%CI=1.23-2.17, P <0.01). There were similar results with obesity related phenotypes, with the genecomprehensive lifestyle behaviors interactions were significant ( P gene×lifestyle behaviors <0.05). Conclusion The present study suggests the interactive effect of rs 7498665 polymorphism located in the SH2B1 and unhealth lifestyle on childhood obesity and related phenotypes.

Objective: To investigate the associations between single nucleotide polymorphisms of UDP glucuronosyltransferase Family 1 Member A1 ( UGT1A1 ) with non alcoholic fatty liver disease (NAFLD) and levels of serum lipids in Beijing children, and to provide scientific evidence for the study of genetic mechanism. Methods: In total, 1 027 children aged 7-18 years were recruited from two primary schools and three middle schools from Haidian district of Beijing, who were randomly assigned to case group ( n =162) and control group ( n =865). General condition and medical history were collected by trained field health workers. Height, weight and liver ultrasound were examined. Additionally, fasting venous blood were collected to detect serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and alanine aminotransferase (ALT). The single nucleotide polymorphisms (SNPs) of UGT1A1 were genotyped. Binary logistic regression and multiple linear regression were applied to analyze the associations between three SNPs of UGT1A1 and NAFLD, ALT and levels of serum lipids. Results: The SNP rs 10929303 (C>T) of UGT1A1 was negatively associated with NAFLD( OR=0.51, 95%CI=0.32- 0.83 , P =0.01), while the SNP rs 4148323 (G>A) was negatively associated with the serum level of TC ( B=-0.10, 95%CI=-0.19- -0.02 , P =0.02); in addition, results were consistent regardless of whether the TC level was measured using a categorical variable or continuous variable. Conclusion The SNP rs 10929303 of UGT1A1 is associated with NAFLD, and the SNP rs 4148323 of UGT1A1 is associated with TC levels in Beijing children.

Objective: To examine the association between polymorphism of rs10185316 in insulin-induced gene 2 (INSIG2) and blood pressure among children and adolescents. Methods: 9 junior middle schools in Dongcheng District of Beijing and 5 schools (3 primary junior middle schools, 2 primary schools) in Haidian District of Beijing were chosen in 2005 and 2007, respectively. According to the Chinese BMI percentile criteria for screening overweight and obesity in school children, we recruited 1 425 overweight or obese children and 605 normal weight children. A total of 2 018 students with complete data of blood pressure and genotype data were included in this study. According to the blood pressure criterion of children and adolescents, 702 participants were categorized into high blood pressure group and 1 316 into normal blood pressure group. Participants' information of gender, age, height, weight and blood pressure were collected by questionnaire and physical examination. Genomic DNA was extracted from peripheral blood sample for genotyping of INSIG2 rs10185316 polymorphism. Multiple linear regression was conducted to analyze the associations between rs10185316 polymorphism in INSIG2 and SBP, DBP, mean arterial pressure (MAP) and pulse pressure. Results: The age, BMI, SBP and DBP of the high blood pressure group were separately (14.3±1.4) years old, (27.3±4.2) kg/m², (130.5±10.9) and (76.7±13.3) mmHg (1 mmHg=0.133 kPa), all higher than that of the normal blood pressure group, which were (12.2±2.9) years old, (22.0±4.0) kg/m², (104.4±10.9) and(54.6±15.2) mmHg, respectively (all P values<0.001). After age, sex, district and BMI adjusted, compared with the participants carrying INSIG2 rs10185316 CC genotype, CG/GG genotype carriers had lower DBP (β(95%CI):-1.67(-2.84--0.50), P=0.005), higher PP(β(95%CI): 1.91(0.61-3.20), P=0.004), and lower MAP(β(95%CI):=-1.03(-2.01--0.05), P=0.039). Conclusion INSIG2 rs10185316 polymorphism was associated with DBP, PP and MAP among children and adolescents in an independent way from BMI.

Objective: To study the role of rs 12145833 polymorphism of SDCCAG 8 gene in the intervention of childhood obesity, so as to provide scientific basis for formulating personalized intervention measures based on genetic background in children with obesity. Methods: From September 2018 to June 2019, a total of 393 children aged 8-10 years in Beijing were enrolled in a cluster randomized controlled trial. Eight schools were randomly allocated into intervention group and control group at a ratio of 1∶1. Saliva DNA samples were collected to detect rs 12145833 polymorphism of SDCCAG 8 gene. The intervention group received a comprehensive intervention, while the control group received usual practice. Intervention measures included diet improvement, sports, school amd family sport. The obesity related indicators were measured at baseline and after the end of intervention 1 academic year. Multiple linear regression and Logistic regression were used to analyze the interaction between genes and intervention on obesity indicators. Results: In the intervention group, children with TT genotype of rs 12145833 of the SDCCAG 8 gene had less increase in systolic( β=4.56, 95%CI=1.84-7.28, P <0.01) and diastolic blood pressure( β=2.59, 95%CI=0.45-4.73, P <0.05) than those with GT and GG genotypes. In the control group, the systolic blood pressure of children with TT genotype increased more than those with GT and GG genotype( β=-2.86, 95%CI=-5.63--0.83, P <0.05). There was an interaction between rs 12145833 polymorphism of SDCCAG 8 gene and intervention on systolic blood pressure, diastolic blood pressure and body fat percentage in children( P <0.05). Conclusion Children with TT genotype of rs 12145833 in the SDCCAG 8 gene are more sensitive to obesity intervention than those with GG and GT genotypes, especially in the improvement of systolic blood pressure, diastolic blood pressure and body fat percentage. Further trials to study the role of rs 12145833 polymorphism of SDCCAG 8 gene in the intervention of childhood obesity among different ethnic populations are needed.

Objective: To assess the associations between the single nucleotide polymorphism (SNP) rs 12225230 of salt inducible kinase 3 ( SIK 3) and obesity/central obesity in children, and to provide evidence for screening intervention for obesity in children and adolescents. Methods: A cluster sampling of 2 030 children aged 7-18 years in Beijing were enrolled and height, weight and waist circumference were measured according to the manufacturer. The genotype frequency of SNP rs 12225230 was detected by matrix assisted laser analysis/ionization time of flight mass spectrometry (MALDI TOF MS). Logistic regression and multiple linear regression were applied to analyze the associations between SNP rs 12225230 and overweight/obesity and central obesity. Polyphen2 database was used to predict the effect of SNP rs 12225230 on the protein function of SIK 3. GTEx database was used to explore expression quantitative trait loci (eQTL) of SNP rs 12225230. Results: C allele of SNP rs 12225230 was a risk allele for obesity and severe obesity in children ( OR obesity =1.50, 95% CI=1.10-2.04, P =0.01; OR severe obesity =1.72, 95% CI=1.23-2.39, P <0.01). The SNP rs 12225230 was positively associated with waist circumference and waist height ratio ( β waist circumference =1.40, 95% CI=0.28- 2.52 , P =0.01; β waist height ratio =0.01, 95% CI=0.00-0.02, P =0.01). C allele of SNP rs 12225230 may be harmful to the function of the protein encoded by the SIK 3, and was positively related to the expression of the APOA 1 in the heart tissue. Conclusion SNP rs 12225230 is associated with obesity and central obesity in children, and SNP rs 12225230 may affect the expression of the APOA 1 in children, but its association with lipid metabolism needs to be verified

Abstract In recent decades, the prevalence of childhood obesity has increased at a alarming rate. The health hazards of childhood obesity are substantial, which has become an important public health problem. Lifestyle intervention is an effective means to prevent childhood obesity. However, individuals varied in their response to the intervention program, which may be associated with genetic factors. This paper systematically reviews the research progress of the effects of FTO, MC4R and other genetic variants on childhood obesity interventions, summarizes the limitations of current research and sheds light on the future research, so as to provide scientific evidence for individualized childhood obesity interventions based on genetic backgrounds.

Objective To investigate the association between rs780094 polymorphism in glucokinase regulatory protein (GCKR) and plasma lipid levels in children and adolescents. Methods 1 026 Chinese children aged 7 to 18 years were recruited,with anthropometric measurements,detection of plasma lipid levels and genotyping of rs780094 performed. Relationships between polymorphism and plasma lipid levels were tested,using multivariate linear regression and logistic regression. Results A-allele of rs780094 in GCKR was associated with increased TC,TG and LDL-C levels(b=0.06 mmol/L,P=0.037;b=0.09 mmol/L,P<0.001;b=0.05 mmol/L,P=0.040) under the additive model adjusted for age,age square and gender. The rs780094 in GCKR was also associated with abnormal levels of TG and LDL-C(OR=1.60,95%CI:1.30-1.97,P<0.001;OR=1.35,95%CI:1.02-1.80,P=0.036). Conclusion The rs780094 in GCKR was associated with plasma lipid levels in children and adolescents while A-allele of rs780094 might serve as genetic factor for the increased plasma lipid levels.

【Objective】 To explore the relationship between polygenic risk score (PRS) and the sustainability of childhood obesity intervention, in order to provide scientific basis for future sustainable and personalized childhood obesity intervention based on genetic background. 【Methods】 A total of 148 children with overweight/obesity at baseline were selected as study subjects from a cluster randomized controlled trial (September 2018 to April 2021) regarding the effect of a childhood obesity intervention in Beijing, China. Saliva was collected to detect the whole genome sequencing. Four PRSs were built: weighted and unweighted PRS69, weighted and unweighted PRS67. The interactions between PRS and study arms on the sustainability of intervention effect (the changes in obesity-related indicators between the end of the intervention and the last follow-up) were analyzed. 【Results】 There were interactions between PRS and study arms on the rebound degree of waist circumference adjusted for body mass index (BMI), waist-to-hip ratio adjusted for BMI, and systolic blood pressure after the intervention. Compared with the control group, children in the intervention group carried each additional unit (standard deviation) of weighted PRS69, the waist circumference adjusted for BMI rebounded more by 0.34 (95%CI: 0.05 - 0.63, P=0.020), and waist-to-hip ratio adjusted for BMI rebounded more by 0.29 (95%CI: 0.03 - 0.56, P=0.031) at the last follow-up survey. When children in the intervention group carried each additional unit (standard deviation) of weighted PRS67 and unweighted PRS67, systolic blood pressure at the last follow-up survey rebounded more by 3.58 (95%CI:0.50 - 6.66, P=0.023) and 3.75 (95%CI: 0.78 - 6.71, P=0.014), respectively. 【Conclusions】 The higher PRS (the more risk alleles) children with overweight/obesity carried, their waist circumference, waist-to-hip ratio and systolic blood pressure are more likely to rebound after the intervention. Findings from this study suggest that future studies should focus more on these high-risk children after the intervention to prevent and control obesity rebound.