The Association Of FTO Gene With Obesity And Its Effect On Diet And Physical Activity Among Chinese Han Children

BackgroundGenetic and environmental factors play an important role in the emergence and development of obesity. Genetic factors increase the susceptibility to obesity. However, even in the presence of genetic factors, obesity is the interactive result of various environmental factors and lifestyle. Research on the ralationship between genetic and environmental factors and obesity is significant in the prevention and control of childhood obesity. Recent genome-wide association (GWA) studies identified a group of loci associated with obesity. Among those genes, FTO explained the largest variation of BMI and obesity.The association of FTO genetic variants with BMI and obesity was unequivocally replicated in European and Hispanic populations. However, these associations were controversial with regard to Asian populations. Its still need replicated studies on the associations of FTO rs9939609 with obesity and obesity-related metabolic traits in Chinese population, as well as its interaction with environmental factors, to explore the possible pathway of FTO gene's association with obesity. At the same time, further research on the relationship of genetic and environmental factors is of great significance in the prevention and control of obesity.ObjectivesThe subjects included children aged 7-17 years old and their parents, a subsample of the 2002 China National Nutrition and Health Survey, to explore the associations of FTO rs9939609 with obesity and obesity-related metabolic traits in Chinese children. At the same time, further studies on the interaction of FTO with diet and physical activities can help to explain the role of FTO in governing energy balance and provide scientific basis for further research on the role of genetic factors in the emergence and development of obesity and prevention and control of obesity.Subjects and methods1253 Han children and their mothers'blood of 2002 China National Nutrition and Health Survey saved in-80℃were randomly selected. Genomic DNA was successfully extracted. Taqman-MGB probe method was used to detect the FTO SNP rs9939609 polymorphism.In this study, we further randomly selected 674 Han students aged 8-11 years from the School-based Physical Activity Intervention Research Project launched by National Institute for Nutrition and Food Safety, Chinese Center for Disease Control and Prevention in 2005. The baseline data was used for further study on the associations of FTO SNP rs9939609 with obesity, body composition and obesity-related metabolic traits in Chinese Han children.Logistic regression analysis was performed to compare the likelihood of overweight and obesity between the carriers of TT genotype and the carrier of AA/AT genotype. Association of FTO rs9939609 with obesity-related measures and obesity-related metabolic traits were performed with General Linear Model, using the children's age, sex, family income and puberty stage and mother's age, vocation, education level and area as covariates. The variates of non-normal distributions were natural logarithm transformed before analysis. PAR and PAR% were calculated according to the incidence of obesity.Results1. The associations of FTO gene with obesity and obesity-related metabolic traits in Chinese Han childrenIn 2002 China National Nutrition and Health Survey and School-based Physical Activity Intervention Research Project, the rs9939609 A allele frequency of the Han children of China and Beijing were 12.7% and 12.2% respectively. The frequency of homozygote of the A allele were 1.4% and 1.2%, respectively. And the genotype distributions of FTO SNP rs9939609 were consistent with Hardy-Weinberg equilibrium.No significant associations of rs9939609 with BMI and obesity were found in the 2002 China National Nutrition and Health Survey. This population was powered at 12% to detect odds ratios (OR) of 1.15 for obesity, significantly lower than the study on the Han children in Beijing.The associations of FTO rs9939609 with BMI and obesity in Beijing Han children were confirmed. The prevalence of obesity among the carriers of AA/AT genotypes was significantly higher than that among those with TT genotype (36.4% vs.22.6%, P=0.004). Compared to the carrier of TT genotype, the likelihood of obesity was 1.8 (95% confidence interval (95% CI) 1.2-2.7) for the carrier of AA/AT genotype. The percentage of population attributable risk was 12.4%.Compared with the TT genotype, the weight, BMI, waist-to-hip ratio (WHR), subscapular skinfold thickness, suprailiac skinfold thickness, body fat and lean body mass of carriers with the AA/AT genotype were significantly higher than those with TT genotype. The height, birth weight and percent of body fat were not significantly different between the children with TT and AA/AT genotype.The associations of FTO rs9939609 with triglyceride, adiponectin and glucose were confirmed. While, after further adjustment for BMI, the evidence of associations was reduced. There was weak evidence of associations between rs9939609 and other obesity-related metabolic traits including TC, LDL, HDL, leptin, ghrelin, bloodpressure, insulin, and insulin resistance.2. The associations of FTO gene with dietary energy intake and physical activity levelCompared with the TT genotype, we found marginally increasing level of dietary energy intake in the AA/AT genotype subjects (P=0.095). The consumption of fat, energy from fat and the percentage from fat were found obviously higher. After further adjustment for BMI, the associations were still significant. While, there was weak evidence of associations between rs9939609 and physical activity including physical activity time, sleeping time, sedentary time and energy expenditure of physical activity. After further adjustment for BMI, there were still no significant associations.3. Effects of FTO SNP rs9939609 on DDS, the selection of food and NARCompared with the TT genotype, there was increasing tendency for DDS in the AA/AT genotype subjects. The intra-group diversity scores of cereals and cereal products, meat and meat products, sugars and preserves marginally increased in the AA/AT carriers. There were no significant differences in other intra-group diversity scores.Compared with the TT genotype, the daily intake of tubers, starches and products marginally increased and the daily intake of sugars and preserves obviously increased in the AA/AT carriers. The percentage of energy intake from fruit and fruit products marginally decreased in the AA/AT carriers. While, the percentage of sugars and preserves marginally increased. The selection frequences of food of high energy density (>100kcal/100g or>200kcal/100g or 300kcal/100g) were found obviously higher. After further adjustment for BMI, the differencess were still significant.Compared with the TT genotype, the NAR of energy marginally increased and the NAR of vitamin B6 obviously increased in the AA/AT carriers. And there were no significant differences in the NAR of other nutrients and MAR.4. The association of FTO SNP gene with obesity in Chinese adult womenThe rs9939609 A allele frequency of the Han adult women was 13.6%. The frequency of homozygote of the A allele was 1.8%. And the genotype distributions of FTO SNP rs9939609 were consistent with Hardy-Weinberg equilibrium (P=0.80).The association of FTO rs9939609 with obesity in Chinese adult women was confirmed. No significant association of rs9939609 with BMI was found. The prevalence of obesity among the carriers of AA/AT genotypes was significantly higher than that among those with TT genotype (14.5% vs.9.4%,P=0.O1). Compared to the carrier of TT genotype, the likelihood of obesity was 1.63 (95% confidence interval (95% CI) 1.13-2.44) for the carrier of AA/AT genotype. The percentage of population attributable risk was 12.1%.There was weak evidence of associations between rs9939609 and obesity-related metabolic traits including glucose, TG, TC, LDL, HDL and bloodpressure.No significant differences of dietary energy intake, consumptions of protein, fat, carbohydrate and fiber, energy from protein, energy from fat, energy from carbohydrate and the percentages from protein, fat and carbohydrate between carriers with TT genotype and AA/AT genotype were found. And, there was weak evidence of associations between rs9939609 and physical activity including daily physical exercise time, sleeping time, sedentary time and housework time. 5. The allele frequencies of rs9939609 of FTO gene in Chinese Han children and their mothers and the relation of BMI between Chinese Han children and their mothersThe frequencies of homozygote of the A allele and T allele both in Chinese Han children and their mothers were 0.2% and 65.5%, respectively. The frequency of the AT genotype both in Chinese Han children and their mothers was 12.0%. The rate of both children and their mothers carring at least one dangerous allele was 15.0%. The rate of mothers with at least one dangerous allele and children without A allele was 10.5%. While, the rate of children with at least one dangerous allele and mothers without A allele was 9.0%.After ajustment of the children's age, sex, family income and puberty stage and mother's age, vocation, education level and area, the BMI of mothers was positively related with the children's BMI (P<0.0001) and the correlation coefficient is o.26 (SE=0.02). After further ajustment of the genotype of FTO SNP rs9939609, the BMI of mothers was still positively related with the children's BMI (P<0.0001) and the correlation coefficient is o.25 (SE=0.02).After ajustment of the children's age, sex, family income and puberty stage and mother's age, the correlation coefficient of BMI between Chinese Han children and their mothers was higher in the group of mothers with A allele than the group of mother without A allele. Compared with the group of mother without A allele, there was increasing tendency for the BMI of children in the group of mothers with A allele, but there was no stastically different (P=0.15). And there were no stastical differences in overweight and obesity rate between the two groups (P=0.27 and 0.96, respectively).Further analysis of the relation of BMI between children and their mothers under four different combinations of FTO SNP rs9939609 genotype showed that, the BMI of mothers was positively related with the children's BMI under the four different combinations and the correlation coefficient between children and their mothers both without A allele was smallest. Compared with the group of children and their mothers both with A allele, there was increasing tendency for the BMI of children in the group of children and their mothers both without A allele, but there was no stastically different (P=0.16). And there were no stastical differences in overweight and obesity rate between the two groups, but no statistically significant differenc between anyother two groups (P>0.40). There were no stastical differences in overweight and obesity rate among the four groups (P>0.20).Conclusions1. The rs9939609 A allele frequency was substantially lower in Chinese Han children as compared with the European populations (12 vs.45%).2. The associations of FTO rs9939609 with BMI and obesity are confirmed in Beijing Han children.3. Influence on the energy intake of dietary is one of the ways of FTO gene affects energy balance. However, the effect of FTO SNP rs9939609 on physical activity is not found.4. FTO gene may adjust energy intake through its effect on diet, including food intake and selection of different kinds of food.5. FTO SNP rs9939609 plays a role in the relation of BMI between Chinese Han children and their mothers, but the effect was not significant.