The Relation Between FABP2Gene SNP And Simple Childhood Obesity

Simple childhood obesity without obvious etiologies results fromenergy imbalance, absorbing more calories than needed. In recent years,simple childhood obesity shows an ever-growing trend. It not only hasbecome an important factor affecting the health of children, but also isclosely related to diabetes, cardiovascular and cerebrovascular diseases,hyperlipidemia in their adulthood. High-calorie food is a leading cause ofchildhood obesity, while a nice intestinal absorption as well as imbalancebetween lipid synthesis and catabolism is considered to be the root ofdisease forming. The small intestine is the main organ to human nutritionabsorption. The intestinal fatty acid binding protein (FABP2) is acytoplasmic low-molecular weight apolipoprotein and its expression isconfined to the epithelial cells of the small intestine, which is closelyrelated to the absorption, targeting transport and metabolism of long-chainfatty acids (LCFA). Human FABP2gene has a single nucleotidepolymorphism at codon54of exon2(rs1799883) that results in an alanineto threonine substitution (Ala�'Thr). The mutation of Ala54Thr may affectthe function of the FABP2protein. In the past years, the54T allele hadbeen reported to be associated with disorder of lipid metabolism and insulinresistance, while the relationship between simple childhood obesity andFABP2A54T polymorphism has been little reported. It is still unknownwhether simple childhood obesity is related to FABP2gene A54Tpolymorphism and its expression. we investigated the distributionfrequency of FABP2gene polymorphism and serum biochemical variablesin simple childhood obesity, to explore the relationship between simplechildhood obesity and54T allele polymorphism, the effect of A54T polymorphism on of serum lipids and glucose metabolism; further, toexplore the significance of FABP2in the development of simple childhoodobesity we established young obese rat models.First, A54T genotype and allele frequencies of FABP2gene inoverweight/obesity and control group were detected. According to “BMIclassification criteria for overweight and obesity in children andadolescents” developed by the working group on obesity in China, weselected83subjects with overweight/obesity and100subjects withhealthy/normal weigh in Zhangjiakou. Using polymerase chain reaction(PCR)-restriction fragment length polymorphism (RFLP) technology, theAla54Thr FABP2gene allele and genotype frequencies between controlgroup and overweight/obesity group are detected. DNA sequences wereconfirmed by DNA sequencing. The automatic biochemical analyzer wasused to detect fasting blood glucose (FBG), triglyceride (TG), totalcholesterol (TC), high-density lipoprotein cholesterol (HDL-C) andlow-density lipoprotein cholesterol (LDL-C) levels. Plasma insulin (Ins)level was detected by radiation immune method; free fatty acid (FFA) levelwas tested by ELISA method; and insulin resistance index (HOMA-IR)was also calculated. We analyzed the correlation between FABP2A54Tpolymorphism and the development of children’s obesity. The relationbetween FABP2A54T polymorphism and abnormal blood lipids andinsulin resistance was assessed.Second, we simulated eating habits of obesity children to develop ayoung obese rat model; then the expression levels of FABP2mRNA induodenum, jejunum and ileum tissues of young rats were detected andanalyzed by SYBR Green I real time fluorescence quantitative PCRmethod; the serum biochemical variables were also detected with samemethod; and the correlation between FABP2mRNA expression and childobesity was assessed in rats. The results of study on FABP2gene polymorphism revealed asfollows: in overweight/obese group, the frequency of AA, AT, TTgenotypes was33.7%,49.4%and16.9%, respectively; in control group, thefrequency of AA, AT, TT genotypes was51.0%,40.0%and9.0%,respectively; the difference between two groups was statistically significant（2=6.27，P＜0.05）. In overweight/obese group, the frequencies ofalleles were58.4%for54A and41.6%for54T; in control group, thefrequencies of alleles were71.0%for54A and29.0%for54T; there wassignificant difference（2=6.32，P＜0.05）. The plasma biochemicalvariables results showed that compared with the normal control group,plasma TG (P<0.01), Ins (P<0.05), HOMA-IR (P<0.05) were elevated inoverweight/obesity Group, the difference between two groups wasstatistically significant. At the same time, in overweight/obesity group, thecarriers of TT homozygous genotypes had significantly higher plasma TGlevels than those with AA wild genotypes (P<0.05); A increased tendencyof plasma Ins, FFA levels and HOMA-IR was found in the carriers with TThomozygous genotypes, but no difference compared with those with AAwild genotypes（P>0.05）； Compared with those with AA wild genotypes,related plasma biochemical variables in the carriers with AT heterozygousgenotypes had no differences (P>0.05).The results of study on animal model showed: in both control groupand obesity group, the expression levels of FABP2mRNA were highest inthe ileum, intermediate in the jejunum, and lowest in the duodenum, therewere significant differences among them(P<0.05). Compared with controlgroup, the expression levels of FABP2mRNA in obesity group weresignificantly decreased (P<0.05); and the levels of serum TG in the obesitygroup were significantly higher (P<0.01).In conclusion, the FABP2gene A54T polymorphism is related tosimple childhood obesity; the allele encoding54T in FABP2gene may be apotential factor contributing to promoting lipid metabolism abnormality and insulin resistance; the individuals with54T alleles may be increasedrisk for obesity and dyslipidemia. FABP2gene expression levels ofdifferent anatomical segments in the small intestinal tissue have differences;a high-fat diet significantly reduced mRNA levels of FABP2in the smallintestinal tissue of rats, made the weigh gain and elevated serum TG levels;it suggests that FABP2involves in lipid metabolism, and may have acertain relationship with the development of childhood obesity.The finding provides experimental and theoretical foundations forfurther studies on FABP2gene-nutrient interaction and regulationmechanism of gene expression. It also provides a basis for childhoodobesity prevention and targets of gene therapy.