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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 3502 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,1196 central obese cases and 2306 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,MC4Rrs 17782313-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.
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Objective@#The present study aimed to prospectively validate whether the single nucleotide polymorphisms (SNPs) in obesity-related genes were associated with change in body mass index (BMI) and obesity status during childhood.@*Methods@#Based on the Beijing Child and Adolescent Metabolic Syndrome study (BCAMS), which was initiated between April and October in 2004, we conducted a follow-up study among 1 624 children aged 6 to 11 years old with genetic data in December 2010. A total of 777 children (246 obese and 531 non-obese) were reassessed for BMI. Z-score of BMI was used to standardize for age and sex. The changes in BMI Z-score during follow up were calcnlated SNPs were genotyped by quantitative Real-time PCR (rs9939609, rs6499640, rs7138803, rs1805081, rs17782313, rs6265, rs10938397, rs6235, rs29941, rs2844479, rs10913469 and rs4788102). Overweight and obesity were diagnosed by the age-and sex-specific BMI cutoffs recommended by the International Obesity Task Force. A multilocus genetic risk score for BMI was calculated as the simple sum of alleles of all the SNPs associated with BMI. Linear regression models and logistic regression models were performed to assess the associations of change in BMI Z-score and obese status with genotypes (assuming an additive model), respectively.@*Results@#During 6 years of follow-up, 158 previously obese children remained obese as they aged into adolescence, and 88 transiently obese children were not obese during the second survey, 58 children were newly identified obese, and the other 473 children remained their non-obese state. BMI Z-score increased from 1.41±0.05 at baseline to 1.57±0.06 at follow up.The genotypes of the SNPs except rs6499640(P=0.033) and rs6265(P=0.041) were in Hardy-Weinberg equilibrium in each group (P>0.05). Each additional copy of the rs9939609 A allele was significantly associated with an increase in BMI Z-score (β=0.205, P=0.014) during follow up. Per C allele of rs17782313 was associated with an increase in BMI Z-score at baseline (β=0.268, P=0.003). As the non-obese reference, a significantly relative risk of obesity at follow up was observed for children carrying rs9939609 A-allele versus the T-allele carriers (OR=2.37, 95%CI: 1.45-3.88, P=0.001). Rs17782313 C-allele was significantly increase the risk of obesity only at baseline (OR=1.79, 95%CI: 1.24-2.60, P=0.002). Rs1805081 A-allele was significantly associated with durative of obesity (OR=1.45, 95%CI: 1.04-2.03, P=0.028). Each unit higher genetic risk score was associated with increases risk of 0.18 times (OR=1.18, 95%CI: 1.05-1.33) in childhood transient obesity, and 0.22 times (OR=1.22, 95% CI: 1.06-1.42) in incident obesity at follow-up. But it was not significantly associated with persisted obesity during 6 years of follow-up (OR=1.09, 95% CI: 0.99-1.20).@*Conclusion@#We confirmed that the change of BMI and obesity status in children was affected by different genetic factors. Individual who carries more risk alleles in obesity-related genes may increase the susceptibility to obesity.
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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 3502 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,1196 central obese cases and 2306 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,MC4Rrs 17782313-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.
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Objective To systematically evaluate the associations between SEC16B polymorphisms and body mass index (BMI) or risk of obesity in different ethnic populations.Methods A literature retrieval was carried out by using Wanfangdata,Chinese National Knowledge Infrastructure (CNKI),China Science and Technology Journal Database (VIP databases),PubMed,Embase,Web of Science,NIH GWAS catalog databases to collect the research papers published between 2009 and 2015 on the associations between SEC16B polymorphisms and BMI or risk of obesity.Summary beta estimates (βs),odds ratios (ORs) and 95％ confidence intervals (CIs) were calculated to assess the strength for the BMI analyses and obesity status.Meta-analysis was performed with Stata 12.0 software.Results Totally 15 papers for rs10913469 and 13 papers for rs543874 were included in this Meta-analysis.Under additive genetic model,rs10913469 and rs543874 in SEC16B gene were positively associated with BMI,and the combined β was 0.04 (95％CI:0.03-0.05) and 0.03 (95％CI:0.02-0.04),respectively,and rs10913469 and rs543874 were also associated with the risk of obesity,and the combined OR was 1.11 (95％CI:1.08-1.15) and 1.28 (95％CI:1.20-1.36),respectively.There were no significant differences among subgroups of ethnicity,different age groups and literatures with different quality.Conclusion rs10913469 and rs543874 in SEC16B gene are significantly associated with BMI and the risk of obesity,and C allele ofrs10913469 and G allele ofrs543874 increase the risk for obesity in different ethnic populations.
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Objective To systematically evaluate the associations between SEC16B polymorphisms and body mass index (BMI) or risk of obesity in different ethnic populations.Methods A literature retrieval was carried out by using Wanfangdata,Chinese National Knowledge Infrastructure (CNKI),China Science and Technology Journal Database (VIP databases),PubMed,Embase,Web of Science,NIH GWAS catalog databases to collect the research papers published between 2009 and 2015 on the associations between SEC16B polymorphisms and BMI or risk of obesity.Summary beta estimates (βs),odds ratios (ORs) and 95％ confidence intervals (CIs) were calculated to assess the strength for the BMI analyses and obesity status.Meta-analysis was performed with Stata 12.0 software.Results Totally 15 papers for rs10913469 and 13 papers for rs543874 were included in this Meta-analysis.Under additive genetic model,rs10913469 and rs543874 in SEC16B gene were positively associated with BMI,and the combined β was 0.04 (95％CI:0.03-0.05) and 0.03 (95％CI:0.02-0.04),respectively,and rs10913469 and rs543874 were also associated with the risk of obesity,and the combined OR was 1.11 (95％CI:1.08-1.15) and 1.28 (95％CI:1.20-1.36),respectively.There were no significant differences among subgroups of ethnicity,different age groups and literatures with different quality.Conclusion rs10913469 and rs543874 in SEC16B gene are significantly associated with BMI and the risk of obesity,and C allele ofrs10913469 and G allele ofrs543874 increase the risk for obesity in different ethnic populations.
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<p><b>OBJECTIVE</b>To analyze the trends on the prevalence rates of obesity and cardiometabolic among children and adolescents in Beijing, during 2004-2013.</p><p><b>METHODS</b>Data was collected from three cross-sectional studies among children and adolescents, aged 7-17 years old in Beijing. Two studies in 2004 and 2013 were conducted in general population, and one was among obese children in 2007. Data on anthropometric measurements including weight, height, and age was collected from all the subjects. The obese children from all three studies underwent a clinic examination that containing blood pressure, fasting plasma glucose, lipid profile (TC, TG, LDL-C, HDL-C), and acanthosis nigricans. Liver transaminases detection (ALT and AST) and liver ultrasound examination were performed in obese children from surveys in 2007 and 2013.</p><p><b>RESULTS</b>The prevalence of severe obesity increased from 1.86% in 2004 to 4.17% in 2013, with an annual increase rate as 0.26%. The proportion of severe obesity in obesity increased from 18.92% in 2004 to 25.15% in 2013. After adjusting for age and gender, the prevalence of IFG, hypertriglyceridemia and low HDL-C in both obese children and adolescents increased during 2004-2013 (all P < 0.05). The prevalence rates of hypertension, dyslipidemia, hypertriglyceridemia, and acanthosis nigricans in severe obese children were higher than those in moderate obesity. The proportion of children with 2 or more cardiometabolic risk factors in severe obese children was higher than in moderate obese children.</p><p><b>CONCLUSION</b>The prevalence rates of obesity and cardiometabolic risk factors among children and adolescents in Beijing showed an increase during 2004-2013.</p>
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Adolescent , Child , Female , Humans , Male , China , Epidemiology , Pediatric Obesity , Epidemiology , Prevalence , Risk FactorsABSTRACT
<p><b>OBJECTIVE</b>To examine the impact of single nucleotide polymorphisms in obesity-related genes on risk of obesity and metabolic disorder in childhood.</p><p><b>METHODS</b>A total of 3 503 Chinese children aged 6 to 18 years participated in the study, including 1 229 obese, 655 overweight and 1 619 normal weight children (diagnosed by the Chinese age- and sex- specific BMI cutoffs). Body size parameters were assessed and venipuncture blood samples were collected after a 12-hour overnight fast. Plasma glucose, insulin and serum lipid profiles were measured.Genomic DNA was isolated from peripheral blood white cells using the salt fractionation method. A total of 11 single nucleotide polymorphisms were genotyped by TaqMan allelic discrimination assays with the GeneAmp 7900 sequence detection system (Applied Biosystems, Foster City, CA, USA) (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397, FAIM2 rs7138803, BDNF rs6265, NPC1 rs1805081, PCSK1 rs6235, KCTD15 rs29941, BAT2 rs2844479, SEC16B rs10913469 and SH2B1 rs4788102). Multiple factor analysis was performed to estimate the association between the variant and obesity-related traits. The false discovery rate (FDR) approach was used to correct for multiple comparisons.</p><p><b>RESULTS</b>After sex, age and pubertal stage adjustment and correction for multiple testing, the rs9939609-A, rs17782313-C, rs10938397-G, and rs7138803-A alleles were associated with higher BMI (β = 0.352-0.747), fat mass percentage(β = 0.568-1.113), waist circumference (β = 0.885-1.649) and waist-to-height ratio(β = 0.005-0.010) (all P values < 0.01) in Chinese children. The rs6265-G allele increased BMI(β = 0.251, P = 0.020). The rs9939609-A, rs17782313-C, and rs10938397-G and rs6265-G alleles were also associated with risk of obesity (OR = 1.386, 95%CI:1.171-1.642; OR = 1.367, 95%CI:1.196-1.563; OR = 1.242, 95%CI:1.102-1.400; OR = 1.156, 95%CI:1.031-1.296).Rs7138803 was associated with risk of obesity only in boys (OR = 1.234, 95%CI:1.043-1.460). GNPDA2 rs10938397-G allele was associated with risk of insulin resistance(OR = 1.205, 95%CI:1.069-1.359), but there was no significance after adjusting for BMI.</p><p><b>CONCLUSION</b>The association of FTO rs9939609-A, MC4R rs17782313-C, GNPDA2 rs10938397-G, and FAIM2 rs7138803-A with higher BMI, fat mass percentage, waist circumference, and waist-to height ratio and risk of obesity, and BDNF rs6265-G allele may increase BMI and obesity risk in Chinese children. GNPDA2 rs10938397-G may increase the risk of childhood insulin resistance depending on BMI.</p>
Subject(s)
Adolescent , Child , Humans , Male , Alleles , Asian People , Body Mass Index , Genetic Predisposition to Disease , Genotype , Metabolic Diseases , Obesity , Overweight , Polymorphism, Single Nucleotide , Risk Factors , Waist CircumferenceABSTRACT
<p><b>OBJECTIVE</b>To explore the role of adipokines including insulin, resistin, leptin, adiponectin, acylation stimulating protein (ASP) and complement C3 (C3) in various types of obesity (peripheral obesity, abdominal obesity and mixed obesity) in Chinese children and adolescents, and their relationships with body size and pubertal development.</p><p><b>METHODS</b>Children and adolescents (n=3 508) aged 6 to 18 years, with 1 788 boys and 1 720 girls were assessed for body mass index, waist circumference, pubertal development, blood insulin, resistin, leptin, adiponectin, ASP and C3 levels. Three types of obesity [peripheral obesity (n=43), abdominal obesity (n=473), mixed obesity (n=1 187)] and non-obese control (n=1 805) were defined with combined use of Chinese body mass index and waist circumference criteria.</p><p><b>RESULTS</b>Serum resistin, leptin and adiponectin levels were higher in girls than those in boys (all P<0.01). Insulin and leptin increased and adiponectin decreased across five Tanner stages in both girls and boys (all P<0.001), while ASP changed only in girls (P<0.001) and C3 only in boys (P<0.001). Insulin, leptin and ASP were higher, but adiponectin was lower in all three types of obesity vs. the non-obese control (all P<0.05). The greatest abnormalities of all six adipokines were found in the mixed obesity group. With inclusion of body mass index and waist circumference in simultaneous regression analyses, both body size indices were independently and significantly correlated with insulin, leptin and adiponectin after age and gender adjustment. Compared with waist circumference, the body mass index was stronger in interpreting insulin, leptin, adiponectin and ASP levels, whereas it was weaker in explaining variance of plasma C3.</p><p><b>CONCLUSION</b>Obese children have a worse metabolic profile with high insulin, resistin, leptin, ASP and C3, and low adiponectin levels. The adipokine profile in mixed obesity is worse than that in peripheral or abdominal obesity. Identification of obese subjects with a malignant adipokine profile using a combination of body mass index and waist circumference is important for the prevention of obesity-related disease.</p>