Survey Of Lipids Levels In Adolescents And Association Studies Between FTO Gene And Risk Factors Of Non-lipid Cardiovascular Disease

BackgroundIn recent years, obesity in children is prevalent in the world. Obesity, hypertension, high blood glucose and lipid metabolism disorders, as the characteristics of metabolic syndrome (MS), is gradually increasing in children. The form of our country is also not optimistic. As continuous development of clinical research in metabolic syndrome, the status of lipid metabolism disorders in MS is increasing. The International Diabetes Federation (IDF) premised the new definition for MS on central obesity. The abnormity of high density lipoprotein cholesterol (HDL-C) and triglyceride (TG) separated into independent components of MS. That protruded the importance of lipid metabolism disorders in insulin resistance (IR) and predicting the risk of cardiovascular disease (CVD). But at present, there is no uniform criterion for children’s lipid spectrum. Lipid metabolism disorders are interrelated with race and region. The fatty mass and obesity-associated (FTO) gene was the first gene discovered by the whole gene association analysis (GWAS). Since then, domestic and foreign scholars had done a lot of research on correlation of FTO and obesity, hypertension, glucose metabolism disorders and other metabolism related factors. But the research conclusions are different, and it needs to be further studied.Aim1. To investigate the lipid levels of Han Chinese children of school-age, and provide objective data for the formulating of the prevention and management strategy of dyslipidemia in children and adolescents.2. To analyze and compare the predictive effect of various lipid metabolic disorders on the non lipid cardiovascular risk factors and provide evidence for the prevention and treatment of CVD in Chinese children and adolescents.3. To study the polymorphism of FTO gene and the correlation between SNPs and the risk factors of CVD in children and adolescents.Subjects and Methods1.20191 children (10669 boys and 9522 girls) aged 7-16 years old from 6 representative geographical areas, including Beijing, Tianjin, Shanghai, Hangzhou, Nanning, and Chongqing, were surveyed in a random cluster sample in Chinese. Fasting blood triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured. Then non-high-density lipoprotein cholesterol (non-HDL-C) levels were calculated. Data collection, entry, and collation were unified. Then according to age, gender, geographical and other factors, the distribution of blood lipids in the Han nationality children and adolescents were analyzed. Using the receiver operating characteristic curve (ROC-curve) analysis method, to find the most predictive index of various lipid metabolic disorders on non lipid cardiovascular risk factors in children and adolescents.2. Select 851 children aged 7-16 years in the Han nationality, using MALDI-TOF mass spectrometry, detect the single nucleotide polymorphisms of FTO gene (rs10852521, rs17817449, rs1421085, rs8050136, rs3751812 and rs9939609). Study the correlation between SNPs and the risk factors of CVD in children and adolescents.Results1. In ages of 7-16-year-old teenages, the dependablity analysis of HDL-C and age shows statistically significant (P<0.01, r=-0.274). With age increasing, HDL-C shows a downward trend. The other 4 lipid parameters (TC, LDL-C, non-HDL-C, TG) were not significantly related to age. Single and multiple lipid abnormalities in obesity group are significantly higher than those in non-obese group, the difference is statistically significant (P<0.01). The blood lipids of children and adolescents in the eastern region are better than that in the north and the mid-western regions. According to the abnormal lipid standards of the American Academy of Pediatrics, the incidence rate of high TG, TC, LDL-C, non-HDL-C are 9.4%,5.4%,2.2%,4.8%, the incidence rate of low HDL-C is 8.6%.2. ROC curve analysis shows that all 5 lipid indexes can well predict the risk of central obesity. In addition to TC, TG, non-HDL-C, LDL-C and HDL-C are able to predict the risk of hypertension (P<0.01). TG, LDL-C and HDL-C are able to predict the risk of the abnormal fasting glucose (P<0.01). Whether it is for predicting abnormal of obesity, high blood pressure or fasting blood glucose, the area under the ROC curve of TG is the maximum.3. The frequencies of SNP (rs1421085, rs17817449, rs8050136, rs3751812, rs9939609 and FTO) of the 5 genes were highly consistent with the number of alleles at 15.7%. Multivariate Logistic regression analysis showed that 5 FTO SNP (rs1421085,rs17817449, rs8050136, rs3751812 and rs9939609) were significantly associated with obesity, hypertension and fasting glucose (P<0.05). The SNP rs 10852521 had a certain correlation with obesity (P=0.063), but had no significant correlation with hypertension and fasting blood glucose.Conclusion1. Lipids were influenced by many factors. TG, TC, LDL-C and non-HDL-C are not affected by age in children and adolescent. However, HDL-C has a tendency to decrease with age. Serum lipid levels in children and adolescents are significantly better than that in obesity group. Serum lipid levels in children and adolescents of eastern region are better than that of the north and the mid-west.2. Compared with other lipid indexes, TG is the best predictive index on non lipid CVD risk factors for children and adolescents.3. Single nucleotide polymorphisms of FTO gene are associated with of obesity, hypertension and abnormal glucose metabolism.