ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.