| Objective:In order to explore the risk factors relevant with obesity in children from both gene level and environmental factor including microflora in intestinal, our group carried out case-control strategy to study all above factors in large Hazakh children sample in Xinjiang region. The results of the study will be helpful to reveal pathogenesis of obesity and supplement database information of obesity in different ethnics in China. And it can also be helpful to supply theory basis for causal prophylaxis and control obesity in childhood by public health branch. Methods:A three-step stratified sampling method was used. The northern region of the Tianshan mountains is the main living area of Kazakh ethnic populations in Xinjiang. At the initial stage, different counties of Kazakh residential areas were randomly selected from the region of Yili and Altay (NW Xinjiang). During the second stage of randomized sampling, several townships or districts were randomly selected from each of the counties and cities. At the final stage, children were randomly chosen from the primary schools which belonged to the townships or districts. A set of questionnaires, including demographic information, family history of obesity, outdoor activities, cultural levels of parents, eating speed, birth weight, hours of sleep and hours of watching TV, were collected from the participants. Three independent blood pressure measurements and anthropometric measuremenst, including height, weight, waist circumference and hip circumference, were obtained by trained and certified staff members using tstandard protocols. The method to determine overweight and obesity in this study was defined by the Group of China Obesity Task Force. With the purpose of exploring risk factors associated with overweight and obesity, blood glucose, total cholesterol, high density lipoprotein, low density lipoprotein and triglycerides were determined after overnight fasting using a modified hexokinase enzymatic method (Hitachi automatic clinical analyzer, Model 7060, Japan). High sensitity C-Reactive Protein (hs-CRP) and insulin also were determined by hs-CRP ELISA Kit and Radioimmunoassay Kit respectively assayed with kits from USCNLIFE and Peking north biotechnology research institute. To assessment the degree of insulin resistance, a homeostasis model (HOM) was calculated using the formula, HOMA-IR= (FPG×FIN)/22.5. Written informed consents were obtained from all study participants prior to data collection and measurements. The pattern of pairwise LD between the common (minor allele frequency> 5%) SNPs was measured by D’and r2, and all SNPs of FTO gene were futher genotyped in all subjects by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Real-time fluorescence quantitative PCR (Q-PCR) was used to detecte Bacteroidetes, Firmicutes, and Bact/Firm ratio of DNA from stool of Hazakh children. Results:In total,5,360 Kazak subjects (male 2716 and femal 2644) were randomly enrolled from 14 schools which were predominantly Kazak. The detection rate of obesity and overweight was 4.40%(95%C73.85%～4.95%) and 9.10% (95%CI 8.71%～9.49%), respectively. The detection rate of obesity was difference in different age groups (x2=46.121, P=0.000) and in different gender (x2=4.470, P= 0.035). The detection rate of overweight was difference in different age groups (X2= 47.106, P= 0.000) and in different gender (X2=4.635, P=0.031). The tendency of detection rate of obesity was decrease along with age growing. Waist circumference, hip circumference and waist-to-hip ratio in obesity group were higher than overweight group and normal weight group.There was statistical significance among three groups in waist circumference, hip circumference and waist-to-hip ratio. Our data revealed that there existed a linear correlation between waist circumference, hip circumference and body mass index (BMI). And the similar correlation existed among BMI, SBP and DBP. Individuals with a greater waist-to-hip ratio were more prone to development of hypertension. The genotype distributions of the FTO gene variants were found to be in Hardy-Weinberg equilibrium in control group and case group. There was significant difference in frequencies of AA, AT and TT genotypes between controls and cases (X2=12.78, P=0.002), but the frequencies of AA, AG and GG genotypes between controls and cases was no significant difference (X2=1.781, P=0.410). In the case and control groups, SBP, BMI, waist circumference, HDL, FIN, HMOA-IR and hip circumference of the persons with AA genotype of rs9939609 were differences from those of TT or AT genotypes and the statistical significance was also observed (P<0.05). A allele of rs9939609 was associated with increased BMI with per-allele change of 0.490 kg/m2, increased waist circumference with per-allele change of 0.53cm and decreased HDL with per-allele change of 0.09mmol/L when compared with those not inheriting a risk allele. FPG, FIN and HMOA-IR of the persons with GG genotype of rs9930506 were differences from those of AA or AG genotypes elimination the influence of gender and age and the statistical significance was observed (P<0.05). FPG was increased 0.134mol/L in children who are homozygous for the risk allele(GG) comparing with those were not inherited risk allele. Logistic regression analysis showed that both the A allele of rs9939609 (OR=0.546,95%C70.397-0.752) and G allele of rs9930506 (OR=0.450, 95%C70.236～0.858) were an independent risk factor for overweight or obesity. Pairwise LD was carried out for SNPs respectively, rs9939609 and rs9930506 polymorphisms were in LD and most of the pairwise LD values of the polymorphisms were incomplete linkage equilibrium. Hyplotype based association study indicate that 4 haplotypes was reconsreucted by 2 SNPs and haplotype frequency in case group is different from control group in Kazakh population. The number of Bacteroidetes among obese group, overweight group and control group were (0.33±0.47)X 107copy/ul, (1.37±1.76)X107 copy/ul, (1.50±2.20) X107copy/ul and the difference was statistically significant (F=5.836, P=0.004).The amount of Firmicutes among above groups were (4.70+7.01) X107copy/ul, (2.05+3.01) X107copy/ul, (2.43+4.5) X107copy/ul and there were no difference among three groups (F=0.232, P=0.793).The ratio of Bact/Firm among three groups were (0.48±0.52), (1.03±0.82), (1.06±0.62) and the difference was statistically significant (F=6.483, P=0.002). There were no correlation between genetype of rs9930506 and rs9939609 with the number of Bacteroidetes, Firmicutes and ratio of Bact/Firm (P>0.05). Conclusions:The detection rate of overweight or obesity is mismatched with local economical level. The detection rate of overweight or obesity in boys is higher than girls and the tendency is decreasing along with children growing. And the rate of obesity or overweight from high to low is urban, rural counties and countryside. There is positive correlation between BMI and HOMA-IR. The same result exist between waist circumference and HOMA-IR.The results suggest that BMI, the ratio of waist-to-hip is correlated with blood pressure in Kazak children. Both genetype of AA in rs9939609 and GG in rs9930506 are correlate with overweight or obesity in Kazak children. And haplotype that are reconstructed by SNPs of FTO gene might be associated with obesity in Kazak populations. Both number of Bacteroidetes and ratio of Bact/Firm are correlation with overweight or obesity.Besides, there is no correlation between SNPs of FTO with intestinal micro flora. |
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