"The Association of the Fat Mass and Obesity-Associated (FTO) Gene Polymorphism with Obesity"

Abstract

Obesity is an emerging health hazards that reached alarming levels and contribute to the increased morbidity and mortality worldwide. Egypt is now considered one of the top ten countries in the prevalence of both obesity and type 2 diabetes mellitus (T2DM). Both of obesity and T2DM are the major cores of many medical complications especially the metabolic syndrome (MetS) and cardiovascular complications. Many environmental factors are predisposing to the susceptibility of obesity and T2DM, however we respond differently due to our different genetic background. This emphasizes that genetic variations affect the outcome. Variations in fat mass and obesity associated (FTO) gene were linked to risk of obesity in many European populations but with inconclusive results in other populations. To the best of our knowledge, there are no previous reports about polymorphism of FTO gene and its association with obesity and obesity- related diseases as T2DM and MetS in Egyptian population. Thus, we aimed to investigate the allele frequency and genotype distribution of FTO gene rs9939609 in Egyptian female population. Second, compare its frequency to other previous studied populations' frequencies. Finally, study its association with obesity, IR, T2DM and MetS risk. In order to fulfil these aims, this study was conducted on a total of 141 females divided into: a) Non-obese non-diabetic subjects (n=39). b) Obese non-diabetic subjects (n=15), c) Obese type 2 diabetic patients (n= 87) Stratifying the studied population according to T2DM, 87 were diabetic patients vs 54 without diabetes. According to obesity, 102 were obese (BMI ≥ 30 Kg/m2) and 39 were non-obese with inclusion criteria (BMI <27 Kg/m2). All subjects were assessed for anthropometric and metabolic parameters related to obesity and T2DM. In addition FTO gene rs9939609 was genotyped. Results of the current study can be summarized as follows: 1) Significantly elevated levels of FPG, FSI, HOMA-IR values and apparent dyslipidemia occurrence as well as significantly lower values of QUICKI were observed in obese T2DM group in comparison to non-obese non-diabetic group. 2) The overall minor allele frequency (A) of FTO gene rs9939609 was (0.4). 3) There was significant difference in genotype distribution in obese vs non-obese group under the recessive model, where the AA genotype was significantly more frequent in obese than in non-obese individuals. 4) The AA genotype showed a significantly increased odds ratio (OR) for obesity under the recessive model. 5) The association of genotype distribution with T2DM was significant under both the additive and recessive model with an increased odds ratio (adjusted for age) for diabetes under the additive model when AA genotype was compared to TT genotype as reference and under the recessive model. 6) The association of genotype distribution with MetS was significant under both the additive and recessive model with an increased odds ratio (adjusted for age). 7) Subjects with (AA) genotype have significantly higher ALT levels compared with those having (TA) genotype under the additive model and (TA) plus (TT) genotype combined as one group under the recessive model. In conclusion, this study for the first time demonstrated that genotype (AA) of FTO gene rs9939609 may be one of the risk factors for obesity, T2DM, MetS and being associated with high ALT levels in our studied female subjects. Hopefully, future personalized plans for prevention and treatment of obesity and diabetes in Egyptian population would be attempted based on this study.