| BackgroundObesity and lipid disorders have become the health problems all over the world. Obesity and lipid disorders are the leading risk factors of metabolic syndrome, coronary heart disease and diabetes.In our country, with the improvement of living quality and the changes of life style, the proportion of population suffering from obesity and lipid metabolic disorders is increasing year by year, and so are the concerns for the consequent health problems. At present, obesity and lipid metabolism disorders has become the key to prevention and control of public health in our country.Leptin is the product of obesity gene, it is a hormone secreted by fat cells, and its main role is to regulate the weight, fat and energy metabolism. Leptin functions through its receptors in the hypothalamus, in addition, leptin can also directly function to the peripheral.Brown adipose tissue (BAT) plays a significant role in maintaining energy balance of our body by dissipating energy. It becomes a new target prevent and treatment for obesity and lipid disorders. BAT can dissipate a lot of energy through the mitochondria, which is riched in the BAT cells. The traditional viewpoint is that only the infant has the BAT, the adult don’t have the BAT. However, recent findings using fluoro-labeled2-deoxy-glucose positron emission tomography (18FDG-PET) scanning have shown that normal adult humans have distinct brown fat deposits. A lot of evidences indicate that BAT can produce heat by burning fatty acids, and control lipids clearance by regulating lipoprotein homeostasis, indicating that BAT had powerful capability in energy metabolism, thus its function can’t be neglected.STAT3, which is encoded by a gene located in the long arm of chromosome17, is an important member of the STAT family of proteins,. Former findings indicate that STAT3is closely associated with cell growth, proliferation and apoptosis. These years, researchers have found that STAT3is closely associated with obesity. Leptin can regulate appetite and energy metabolism by inducing STAT3activation in the hypothalamus. Evidence from knockout mouse studies showed that disruption of neural STAT3could cause obesity and thermal dysregulation. Recent research has shown that STAT3can enhance the stability of PRDM16through binding to it, and then control the BAT differentiation. Genetic researches in the Europe population suggested that STAT3polymorphisms might be associated with the risks of obesity, while the observations were inconsistent. Heretofore, no reports had been published on the risk of obesity and metabolic disorders predisposed by the genetic variations of STAT3in Asian population.ObjectiveOur study was designed to investigate whether the polymorphisms of STAT3could confer risks of metabolic disorders and obesity in Chinese Han population.Materials and MethodsThe subjects were randomly recruited from a cohort of1742unrelated ethnic Han Chinese (including702male and1040female) who received a physical examination program in Nanfang Hospital, Guangzhou, China. The metabolic indices and demographic characteristics were measured and collected by specialist in Nanfang Hospital. The diagnosis of lipid metabolic disorders was judged according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria (NCEP-ATP Ⅲ). The information of single nucleotide polymorphisms (SNPs) on rs1053005and rs957970of STAT3were acquired from NCBI (build36, dbSNP b126) and HapMap Project database (release#27). rs1053005was in the3’UTR, and rs957970was in the intron region. SNP genotyping was performed with the method of PCR-based restriction fragment length polymorphism (PCR-RFLP). Primers were designed with the Primer Premier (Version5.0). PCR products were digested by the restriction endonuclease over night. About5%of total samples were randomly selected to be genotyped by sequencing for confirmation. Statistical analysis was performed with the Statistical Package for Social Sciences (version16.0; SPSS Inc., Chicago). The genotype distributions in control groups were tested for Hardy-Weinberg equilibrium. Logistic regression model was used to calculate the odds ratio for case-control study, and covariance analysis was used to evaluate the association between the polymorphisms and quantitative clinical indices, which were adjusted for age and gender when appropriate,.. Haplo Stats (v.1.2.1, Mayo Clinic, Rochester, MN, USA) package was used to calculate the frequencies of haplotypes and their association with the risks of metabolic disorders.Results1. The genetic polymorphisms of STAT3were associated with the risks of general obesity, central obesity and hypertriglyceridemia.(1). rs1053005was associated with BMI and waist circumference1742samples were genotyped successfully, including702males and1040females. The polymorphism rs1053005was associated with BMI and waist circumference (P=0.013; P=0.016, respectively), but was not associated with other metabolic indices. Specifically, AG and GG genotypes at rs1053005had lower BMI and waist circumference compared with AA genotype.Further analysis in dominant model found that the G allele carriers had lower level of BMI and waist circumference compared with AA genotype (P=0.007; P=0.004, respectively). The genotype distributions of rs1053005met HWE in control groups (P>0.05), and case-control studies were further conducted. AG and GG genotype had lower risk of obesity compared with AA genotype (OR=0.49,95%CI:0.30-0.78, P=0.003; OR=0.40,95%CI:0.17-0.93, P=0.034, respectively). The analysis in dominant model found that the G allele carriers had lower risk of general obesity compared with AA genotype (OR=0.47,95%CI:0.30-0.73, P=0.001). The mutant G allele of rs1053005had lower risks of obesity compared with A allele (OR=0.60,95%CI:0.43-0.84, P=0.002). In addition, we also found that GG genotype had lower risk of central obesity compared with AA genotype (OR=0.42,95%CI:0.23-0.79, P=0.007),and G allele had a lower risk of central obesity compared with A allele (OR=0.75,95%CI:0.60-0.95, P=0.01). The analysis in dominant model found that the G allele carriers (GG and AG) had lower risk of general obesity compared with AA genotype.(2). rs957970was associated with the risks of hypertriglyceridemia All samples were genotyped successfully, including702males and1040females. The covariance analysis adjusted for gender and age found rs957970was significantly associated with hypertriglyceridemia (P=0.007), but was not associated with BMt and other metabolic indices. The further analysis in dominant model found that the C allele carriers (CT and TT) had higher level of triglyceride compared with TT genotype (P=0.006). The genotype distributions of rs957970met HWE in control groups (P>0.05), and and case-control studies were further conducted. Rs957970was not associated with the risks of overweight, obesity and hypercholesterolemia (P>0.05), but it was associated with the risks of hypertriglyceridemia. CC genotype had higher risk of hypertriglyceridemia compared with TT genotype (OR=1.43,95%CI:1.07-1.90, P=0.015). The further analysis in dominant model found that the C allele carriers (CT and TT) had higher level of triglyceride compared with TT genotype (OR=1.36,95%CI:1.04-1.79, P=0.027)(3). Haplotypes of rs1053005and rs957970were associated with the risks of overweight and obesityThe carriers with halpotype GT had lower risks of overweight, general obesity and central obesity (OR=0.55,95%CI:0.35-0.86, P=0.003; OR=0.17,95%CI:0.04-0.69, P=0.02; OR=0.31,95%CI:0.14-0.71, P=0.006, respectively). The carriers with halpotype GC had lower risk of general obesity (OR=0.67,95%CI:0.48-0.94, P<0.04). ConclusionsIn our study, genetic polymorphisms of STAT3were associated with the risks of overweight, obesity and hypertriglyceridemia in a Chinese Han population. |
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