Obesity-associated protein (FTO) is an important m6A demethylase that regulates RNA methylation modification and can promote the proliferation of acute myeloid leukemia(AML) cells. FTO regulates the methylation level of AML through multiple cellular signaling pathways such as FTO/RARA/ASB2, FTO/m6A/CEBPA, and PDGFRB/ERK, and participates in the occurrence, development, treatment and prognosis of AML. At present, studies have found that a variety of inhibitors targeting FTO have shown good anti-leukemia effects, and the study of FTO will provide new ideas for the treatment of AML. This review focus on the mechanism of action of FTO in AML and the research progress of FTO inhibitors in AML.
Humans ; Methylation ; Leukemia, Myeloid, Acute/genetics* ; Prognosis ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism*

OBJECTIVETo clarify the contradictory findings in patients with obesity and type 2 diabetes by meta-analysis.

METHODSPubMed and Embase were searched for articles published up to March 2009. All studies on the association of FTO polymorphisms with obesity and type 2 diabetes were included. Pooled odds ratio was calculated using the model of fixed or random effects. Sensitivity analysis was performed to evaluate the stability of meta-analytic results.

RESULTSMeta-analysis suggested that rs9939609 A allele was more significantly associated with obesity risk than T allele (3 studies / 004 cases and 4544 control subjects): random effect odds ratio (OR)=1.28, 95%CI=1.05 and 1.55, P heterogeneity =0.05, I2=66.6%. Similar results were observed in rs8050136 polymorphism (3 studies/2404 cases and 5713 control subjects): fixed effect OR =1.25, 95%CI=1.13, 1.37, P heterogeneity=0.12, I2=51.9%. However, no significant association was found between genetics and risk of type 2 diabetes after control of potential confounders (at least for BMI) either for rs9939609 (fixed effect OR=1.05, 95% CI=0.97,1.13) or for rs8050136 polymorphism (fixed effect OR =1.07, 95%CI: 0.99, 1.16). Furthermore, the sensitivity analysis strengthened our confidence in validity of the association. Conclusion FTO polymorphisms are associated with obesity but not with type 2 diabetes in East Asian populations. Further large-scale studies are required to conclusively establish the association.

Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; Asian Continental Ancestry Group ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Far East ; Humans ; Obesity ; genetics ; Proteins ; genetics ; metabolism

Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; genetics ; Body Mass Index ; Body Weight ; genetics ; physiology ; Female ; Genotype ; Homeodomain Proteins ; genetics ; Humans ; Male ; Obesity ; genetics ; metabolism ; Transcription Factors ; genetics

Recent studies have unequivocally established the link between FTO and obesity. FTO was biochemically shown to belong to the AlkB-like family DNA/RNA demethylase. However, FTO differs from other AlkB members in that it has unique substrate specificity and contains an extended C-terminus with unknown functions. Insight into the substrate selection mechanism and a functional clue to the C-terminus of FTO were gained from recent structural and biochemical studies. These data would be valuable to design FTO-specific inhibitors that can be potentially translated into therapeutic agents for treatment of obesity or obesity-related diseases.
AlkB Homolog 1, Histone H2a Dioxygenase ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; Amino Acid Motifs ; Animals ; Catalytic Domain ; DNA ; metabolism ; DNA Repair Enzymes ; metabolism ; Humans ; Methylation ; Obesity ; genetics ; Proteins ; chemical synthesis ; classification ; genetics ; RNA ; metabolism ; Substrate Specificity

OBJECTIVETo study the association of rs9939609 polymorphism of the fat mass and obesity associated gene (FTO) with overweight or obesity in Hazakh children.

METHODSPCR-restriction fragment length polymorphism was used to determine the rs9939609 polymorphism in 141 patients with overweight or obesity and 138 healthy controls. Height and weight were measured for body mass index (BMI). Serum lipid levels including total cholesterol, triglyceride, high-density and low-density lipoprotein cholesterol, blood pressure, plasma glucose levels, and plasma insulin were also determined.

RESULTSThe genotype distributions of both groups were in the Hardy-Weinberg equilibrium. The frequencies of AA, AT and TT were 0.071, 0.511 and 0.418 in the overweight or obesity group, and 0.029, 0.428 and 0.543 in the controls (Chi-square = 5.74, P= 0.057). However, the frequency of AA+ AT genotype in case group (0.582, 82/141) was higher than that in the controls (0.457, 63/138)(Chi-square = 4.368, P= 0.037). The A allele frequency in the case group (0.326) was higher than that in the controls (0.243) (Chi-square = 4.772, P= 0.029). In both groups, the plasma glucose levels of individuals with AA+ AT genotype (4.88± 0.51 mol/L) was higher than those with TT genotypes (4.68± 0.56 mol/L)(P= 0.026). Logistic regression analysis showed that the A allele of the FTO gene was an independent risk factor for overweight or obesity (OR= 0.527; 95%CI: 0.319-0.869).

CONCLUSIONThe A allele of the fat mass and obesity associated gene might be a risk factor of overweight or obesity in Hazakh children in Xinjiang.

Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; Analysis of Variance ; Case-Control Studies ; Child ; China ; ethnology ; Ethnic Groups ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Obesity ; blood ; genetics ; metabolism ; physiopathology ; Phenotype ; Polymorphism, Genetic ; genetics ; Proteins ; genetics