| BACKGROUND AND OBJECTIVE There is a steady increasement in prevalence of obesity in children and adolescents during recent years. Obesity is not only an independent disease, but also the major risk factor of the common disease, sush as metabolic syndrome, type 2 diabetes, etc. The etiology of obesity in children and adolescents has not been completely understood. Recently, with the development of the high-throughput genotyping technology, more and more candidate genes have been identified as being association with the obesity, but the results as replicated in the different race-ethnic populations were always consistent. In this study, our aim is to study the association of the single nucleotide polymorphisms of two candidate genes (TCF7L2, LPIN2) with the obese children and adolescence.SUBJECTS AND METHODS Subjects were divided into three groups:group one (children and adolescents with obesity), group two (children and adolescents with overweigh); group three (normal body weight group, control group).226 cases (age: 11.93±2.87 years old; weight:77.33±18.97kg; height:156.40±15.51cm; BMI: 29.39±3.33 kg/m2; male/female:149/77) were assigned to group one; 239 cases (age: 13.55±2.11 years old; weight:65.46±10.63kg; height:162.42±9.76cm; BMI:24.63±1.83 kg/m2; male/female:155/84) were assignd to group two; 241 cases (age:14.47±1.29 years old; weight:50.28±7.4kg; height:162.15±7.3cm; BMI:19.07±2.04 kg/m2; male/female:94/147) were assigned to group three.Four parameters (FPG:the fasting plasma glucose, TG:triglyceride, Teh:total cholesterol, Flns:fasting insulin) were evaluated in the present study. The insulin resistance index (HOMA-IR) and the quantitative insulin-sensitivity check index (QUICKI) was calculated to evaluate the insulin resistance. The metabolic profile changes were analysed.Genomic DNA was isolated from peripheral blood leukocytes. The real-time fluorescent quantitative polymerase chain reaction technology (probe:Taqman-MGB) was applied to genotype SNP rs7903146 C/T, SNP rs3745012 A/G. All frequencies of genotype and the allele gene and all distributions of genotype were assessed in different groups.RESULTS (1) The children and adolescents in control group are older than those in group one and two. Female in group one and two are less than in group three. Male in group one and two are more than in group three. Through multiple linear regressions, significant increasing tendency of logHOMA-IR level is found in the three groups (obese>overweight>control)(p<0.001). Significant decreasing tendency of logQUICKI level is found in the three groups (obese<overweight<control) (p＜0.001). The prevalence of hyperinsulinemia and impaired FPG in children and adolescents with normal weight is significant lower than those who are obesity and overweight (hyperinsulinemia:F=119.02,p<0.001, impaired FPG:F=17.04, p＜0.001). Regression analysis showes age is not significantly associated with obesity degree.(2) Transcription factor 7-like 2 gene (TCF7L2):The frequency of allele C and allete T of SNP rs7903146 in obese group is 97.7% and 2.3%, respectively; and that in overweight group is 96.0% and 4.0%, respectively; and that in control group is 96.8% and 3.2%, respectively. No significant difference is found between obese/overweight group and control group (x2＜0.001,p=1.000). No associations between SNP rs7903146 and metabolic changes (BMI,TG,TCH,FPG,Fins) are found (p>0.05). The level of QUICKI in CC genotype is significant lower than in CT genotype (F=9.406,p=0.002). The level of HOMA-IR in CC genotype is significantly higher than that in CT genotype (F=3.996,p=0.046). No significant associations between SNP rs7903146 and the prevalence of hyperinsulinemia, hyperlipidemia and impaired FPG are found.(3) LPIN2:The frequency of allele A and allete G of SNP rs3745012 in obese group is 64.4% and 35.6%, respectively; and that in overweight group is 60.6% and 39.4%, respectively, and that in control group is 59.6% and 40.4%, respectively. No significant difference is found between obese/overweight group and control group (x2=1.033,p=0.309). The level of BMI in GG genotype is significantly lower than that in AA and AG genotype (p=0.042). No associations between SNP rs3745012 and metabolic changes (TG,TCH,FPG,Fins,HOMA-IR,QUICKI) arre found (p>0.05). No associations between SNP rs3745012 and the prevalence of hyperinsulinemia, hyperlipidemia and impaired FPG are found. CONCLUSIONS (1) Tendency to impairment of metabolic changes and insulin resistance found in children and adolescents with obesity may be the risk factors of Type 2 diabetes.(2) The SNP rs7903146 of TCF7L2 gene is associated with insulin resistance and not associated with metabolic changes.(3) The SNP rs3745012 of LPIN2 gene is associated with BMI and not associated with metabolic changes and insulin resistance. |
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