The Combined Effects Of Genetic And Lifestyle Factors On Overweight Among Child And Adolescent In Ningxia

Purpose:Understanding of the genetic basis of obesity has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of FTOrs9939609, rs9935401 FTO, MC4 R rs12970134 and MC4 R rs17782313 genetic and lifestyle factors on risk of obesity in order to inform strategies for prevention.Methods :3431 subjects in 15 primary schools and 10 middle schools who came from Jingyuan Yuanzhou, Haiyuan, Xiji and Tongxin county, Ningxia were selected using random stratified cluster method. On the basis of this investigation, 200 overweight/obesity subjects and 200 healthy control subjects were selected using the case-control study. Monitoring projects include:(1) Physical examination(height, weight, chest circumference, waist circumference).(2)Clinical features examination(blood pressure, body fat content, basal metabolism).(3)Questionnaire survey(general conditions, life, studying and physical exercise time, and personal dietary habits survey).(4)Magnetic beads method was used for extracting and purifying genomic DNA. Genotyping for all SNPs was performed using Mass ARRAY technique. t test were used to evaluate the distribution of the continuous variables between cases and controls, Chi-square test were used to evaluate the distribution of the classification variables between cases and controls. Hardy- Weinberg equilibrium for all SNPs was tested by goodness–of–fit test chi-square analysis. Linkage disequilibrium between SNPs and haplotype were tested using genetic analysis software SHEsis. Generalized multifactor dimensionality reduction method(GMDR) was used to analysis gene(environment) and(environment) interaction. The effects of genetic and lifestyle factors for overweight using the logistic regression model for risk assessment.Results :①Compared with control group, there were significantly longer one week screen time, lower frequency of high-strength physical activity, lower frequency of fruit intake, lower frequency of whole grains intake, lower pure milk intake, and lower frequency of nuts intake than cases group(P<0.05). The relatively frequency of fried food intake and frequency of sweets intake were significantly higher when compared with the control group improved(P <0.05).②Logistic regression analysis indicated that the dietary behavioral factors were significantly associated with overweight risk. ORs for high-strength physical activity was 0.322(95% CI: 0.153 ~ 0.677), for fruit intake frequency was 0.325(95% CI: 0.150 ~ 0.707), for nuts intake frequency was 0.228(95% CI: 0.094 ~ 0.553), for screen time was 4.115(95% CI: 1.795 ~ 9.436), for fried food frequency was 5.419(95% CI: 2.276 ~ 12.904), and for fried food intake was 2.613(95% CI: 1.139 ~ 5.997).③Univariate analysis indicated that the carriers TT, TA/AA genotype and T,A allele frequencies distribution at FTO rs9939609 were significant between the case and control group(P<0.05); A allelic gene(OR=1.786, 95% CI: 1.786 ~ 2.770). The carriers GG, GA/AA genotype and G, A allele frequencies distribution at FTO rs9935401 were significant between the case and control group(P<0.05); A allelic gene(OR=1.671, 95% CI: 1.671 ~ 2.603). The carriers GG, GA/AA genotype and G, A allele frequencies distribution at MC4 R rs12970134 were significant between the case and control group(P<0.05); A allelic gene(OR=1.519, 95% CI: 1.519 ~ 2.164). The carriers TT, TC/CC genotype frequencies distribution at MC4 R rs17782313 were significant(P<0.05); but there were no significant differences in the frequencies of the alleles at rs17782313 site between the two groups(P>0.05).④GMDR analysis indicated that(FTO rs9939609, MC4 R rs1297013, MC4 R rs17782313) model indicating a potential gene–gene interaction(P<0.05). Logistic regression analysis showed that FTOrs9939609, MC4Rrs12970134, MC4Rrs17782313 model(TA + AA)-(GA + AA)-(TC + CC) genotype was associated with higher overweight risk(OR = 2.453, 95% CI: 1.120 ~ 5.374). SHEsis software analysis results indicateed that(A)-(A) haplotype in FTO rs9939609, FTO rs9935401 model was associated with higher overweight risk(OR=1.689, 95%CI :1.084 ~ 2.631).(T)-(G) haplotype in FTOrs9939609, FTOrs9935401 model was associated with lower overweight risk(OR=0.592, 95%CI : 0.380 ~ 0.922).(A)-(C) haplotype in MC4 R rs12970134, MC4 R rs17782313 model was associated with higher overweight risk(OR=1.487, 95%CI :1.038 ~ 2.130).⑤GMDR analysis indicated that(FTO rs9939609, fried food intake, nuts intake frequency) model indicating a potential gene–environment interaction(P<0.05). Logistic regression analysis showed that FTOrs9939609(TA+AA), fried food intake≥50 gram per day, nut intake frequency<3 times was associated with higher overweight risk(OR=19.381,95%CI:4.278 ~ 87.797,P<0.05).Conclusion:①High-strength physical activity, fruit intake frequency,nuts intake frequency might be the protective factor in overweight; screen time, fried food frequency, fried food intake might be the risk factor in overweight.②FTO rs9939609(A) allelic gene、FTO rs9935401(A) allelic gene、MC4R rs12970134(A) allelic gene might be the risk factor in overweight. The interaction on overweight was obtained among FTO rs9939609, MC4 R rs12970134 and MC4 R rs17782313.(A)-(A) haplotype in FTO rs9939609, rs9935401 FTO was associated with higher overweight risk.(A)-(C) haplotype in MC4 R rs12970134, MC4 R rs17782313 was associated with higher overweight risk.(T)-(G) haplotype in FTO rs9939609, rs9935401 FTO was associated with lower overweight risk.③The interaction on overweight was obtained among FTO rs9939609, fried food intake, and nut intake frequency. FTOrs9939609(TA+AA), fried food intake≥50 gram per day, nut intake frequency<3 times was associated with higher overweight risk(OR=19.381,95%CI:4.278 ~ 87.797,P<0.05).Recommendations:Developing the health education and insisting the scientific healthy behavior and diet, that has positive meaning to prevent the overweight and obesity.