Fat Mass And Obesity Associated Gene Variants Research Articles

Role of FTO (Fat Mass and Obesity-Associated) and IRX3 (Iroquois Homeobox 3) gene variants on obesity in Quetta

Obesity has become globally prevalent. The novel studies about long-range interaction between promoter-enhancer sequences of FTO and IRX3 genes SNPs, affects the conversion of adipocytes maturation and hence obesity. This can be implemented in pharmaceutical field. The study was established to investigate the association of FTO and IRX3 SNP and its impact on Quetta subjects. Blood Samples taken from 250 individuals (150 obese and 100 non-obese) after informed consent along with demographic information. Organic method of DNA extraction and ARMS-PCR for genotyping was performed. Data analysis was done by liner regression at 95%confidence interval. Both genes’ SNPs were strongly associated with obesity. The AA genotype of FTO SNP rs8050136 showed 3.48-fold (95% CI: 1.45–8.37, P = 0.013) increased risk and allele A 1.76-fold (95%CI: 1.21–2.57, P = 0.004) comparing with allele C. Similarly, compared with TT or GT genotype the GG genotype of IRX3 SNP rs3751723 displayed 3.22-fold (95%CI: 1.40–7.39, P = 0.018) increased onset of obesity, with the frequency of G allele 1.67-fold (95%CI: 1.15–2.41, P = 0.007). Gender and Social statuses were not significantly associated, the different genotypes affect both male and female; AA = 1.21(95%CI: 0.57–2.55, P = 0.41) and AC = 1.14(95%CI: 0.65–1.98, P = 0.65) respectively. Moreover, only Baloch ethnic group in GG genotype of IRX3 variant display 3.16-times (95%CI: 0.86–11.5, P = 0.08) increase obesity risk. Our study suggested that studied polymorphism of both genes are strongly associated with obesity in Quetta population. Moreover, lack of knowledge about obesity genetics is one of the major hurdles in its management at individual level in Pakistan.

A single FTO gene variant rs9939609 is associated with weight change and insulin resistance improvement in response to a robotic sleeve gastrectomy in individuals with severe obesity.

Genetic mechanisms have been involved in the weight response secondary to bariatric surgery. The aim of our study was to evaluate the effects of the rs9939609 genetic variant on weight loss and metabolic parameters after sleeve gastrectomy. Tertiary hospital. A total of 95 participants were enrolled. Co-morbidities, biochemical evaluation, and anthropometric parameters were registered before and after 3-, 6-, and 12-month follow-up. Genotype of the rs9939609 fat mass and obesity-associated (FTO) gene was evaluated. We grouped the participants into 2 groups: carriers of A allele (TA+AA, 69.5%) and noncarriers of A allele (TT, 30.5%). We detected a statistically significant reduction of blood pressure, biochemical, and anthropometric parameters at 3 times during follow-up. After 6 months, changes of some parameters were greater in non-A allele carriers: weight (-39.6 + 4.0 kg versus -24.6 + 2.8 kg; P = .02), waist circumference (-21.1 + 2.1 cm versus -16.2 + 1.8 cm; P = .04), insulin (-12.3 + .9 mUI/L versus -8.9.1 + .2 mUI/L; P = .02), and homeostasis model assessment of insulin resistance (-3.1 + .1 units versus -2.3 + .1 units; P = .02 ). After 12 months, changes of the aforementioned parameters remained greater in non-A allele carriers. The percentage of participants with diabetes diminished earlier in the non-A allele carriers than A allele carriers at 6-month follow-up. The percentage of participants with diabetes at the end of the study was lower in non-A allele carriers (3.4% versus 12.1%; P = .02). Our data suggest that non-A allele carriers of the genetic variant (rs9939609) of the FTO gene showed a better improvement of anthropometric and insulin levels in non-A allele carriers after a robotic sleeve gastrectomy. Both improvements are associated with a lower percentage of participants with diabetes at 12 months.

Variations in Fat-mass and Obesity-associated (FTO) Genes and Allelic Distribution in Some Selected Ethnic Populations in Niger Delta, Nigeria

Aim: To evaluate variations in FTO genes and allelic distribution in some ethnic populations in Niger Delta, Nigeria.
 Study Design: Case-controlled observational study.
 Place and Duration of Study: Federal Medical Centre, Asaba, Delta State and Safety Molecular Pathology Laboratory, Enugu, Nigeria, between March 2020 and February 2022.
 Methodology: The association between sixteen (16) Single Nucleotide Polymorphisms in the FTO gene and some biomarkers of obesity and type 2 diabetes subjects (78 cases and 20 controls) from four different tribes in the Niger Delta region, Nigeria. Multistage sampling method was employed in the subject selection. The subjects were first separated into two groups – new cases (less than a year of diagnosis as Diabetic) and old cases (one year & above). Equal number of samples was then randomly collected from each of the cluster groups. Ten millilitres of blood were collected into EDTA for genotyping using Illumina NextSeq 2000 sequencing platform. Hardy-Weinberg Equilibrium statistical test was used to determine the variation in distribution of the alleles and genotypes within the study population while allelic frequencies were calculated by gene counting. Chi-square (and fisher’s test where chi-square was not applicable) and Odd Ratio (OR) were performed to determine the significant differences and associated risks respectively of the allelic and genotypic frequencies of Type 2 diabetic (T2D) and non-diabetic subjects of the FTO gene variants.
 Results: The results of Hardy-Weinberg Statistical Test, Genotype and Allelic Distribution of FTO gene Variants in Obese/T2D Subjects in Different Tribes of Niger Delta are presented in Tables(1-4) for rs73609956 (C>T), rs116753298 (T>C), rs201041270 (A>G), rs531215275 (A>C), rs146056278 (C>T), rs1410999299 (G>A), rs79206939 (A>G), rs145884431(G>A), rs61743972 (G>A), rs201496428 (C>T), rs146138389 (T>C), rs886052102 (A>G), rs144743617 (G>A), rs886052103 (T>A), rs9939609 (A>T) and rs8050136 (A>C). However, no significant differences in analyzed genotype frequencies were found between T2D and healthy controls.
 Conclusion: Knowledge of the dominant SNPs in some ethnic groups, may provide platform to delay its expression through informed wise choice of lifestyle change and proper dieting.

Association of lipid metabolism-related metabolites with overweight/obesity based on the FTO rs1421085.

Globally, obesity is a severe health issue. A more precise and practical approach is required to enhance clinical care and drug development. The FTO (fat mass and obesity-associated) gene variant rs1421085 is strongly associated with an increased susceptibility to obesity in numerous populations; however, the precise mechanism behind this association concerning metabolomics is still not understood. This study aims to examine the association between metabolites and obesity-related anthropometric traits based on the variant FTO rs1421085. This study was based on a case-control design involving a total of 542 participants including overweight/obese cases and healthy controls. The blood samples were collected from all the participants. The isolated serum samples were subjected to untargeted metabolomics using GC-MS. The isolated DNA samples were genotyped for the FTO rs1421085 variant. Initially, a total of 42 metabolites were identified on GC-MS, which were subjected to further association analyses. The study observed a significant association of two metabolites, glycerol and 2,3-dihydroxypropyl stearate with FTO gene variant rs1421085 and obesity-related anthropometric traits including % BF, WHtR, WC, and HC. The CT genotype of FTO rs1421085 may greatly increase the risk of overweight/obesity by changing the lipid metabolism-related metabolites. Therefore, this study highlights the significance of biochemical networks in the progression of obesity in carriers of the FTO rs1421085 risk genotype.

Association among Body Mass Index, Genetic Variants of FTO, and Thyroid Cancer Risk: A Hospital-Based Case-Control Study of the Cancer Screenee Cohort in Korea.

PurposeObesity has been determined to be associated with fat mass and obesity-associated (FTO) gene and thyroid cancer risk. However, the effect of combined interactions between obesity and the FTO gene on thyroid cancer needs further investigation. This study aimed to examine whether interactions between body mass index (BMI) and the FTO gene are associated with an increased risk of thyroid cancer.Materials and MethodsA total of 705 thyroid cancer cases and 705 sex- and age-matched normal controls were selected from the Cancer Screenee Cohort in National Cancer Center, Korea. A conditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the measure of associations and the combined effect of BMI and FTO gene on thyroid cancer.ResultsBMI was associated with an increased risk of thyroid cancer in subclasses of overweight (23–24.9 kg/m2; adjusted OR, 1.50; 95% CI, 1.12 to 2.00) and obese (≥ 25 kg/m2) (adjusted OR, 1.62; 95% CI, 1.23 to 2.14). There were positive associations between the FTO genetic variants rs8047395 and rs8044769 and an increased risk of thyroid cancer. Additionally, the combination of BMI subclasses and FTO gene variants was significantly associated with thyroid cancer risk in the codominant (rs17817288), dominant (rs9937053, rs12149832, rs1861867, and rs7195539), and recessive (rs17817288 and rs8044769) models.ConclusionFindings from this study identified the effects of BMI on thyroid cancer risk among individuals carrying rs17817288, rs9937053, rs12149832, rs1861867, rs7195539, and rs8044769, whereas the effects of BMI may be modified according to individual characteristics of other FTO variants.

FTO variants are associated with ANGPTL4 abundances and correlated with body weight reduction after bariatric surgery

BackgroundThe FTO (fat mass- and obesity-associated) gene variant is an established obesity-susceptibility locus. FTO protein is a nucleic acid demethylase and FTO genetic variants form long-range functional connections with IRX3, which regulates fat mass and metabolism in humans. From our previous results, we found FTO regulates the metabolism of triglyceride in adipocytes through demethylating Angptl4 (angiopoietin-like protein 4) mRNA in mice. We hypothesized that the FTO genetic variants regulate ANGPTL4 abundances in human adipose tissues and affect the outcome after bariatric surgery. Methods and resultsWe recruited 188 obesity subjects with body mass indices (BMI)>35kg/m2 and 102 non-obese subjects with BMI<30kg/m2 from the OCEAN registry between 2011 and 2014. The distribution of FTO variants rs9939609 among participates was 73.79% TT, 23.79% AT, and 2.41% AA. The subjects with FTO variants AA or AT were correlated with higher BMI than those with FTO variants TT. The serum ANGPTL4 levels were significantly higher in obese subjects and positively correlated with the presence of FTO AA or AT haplotype. Of these participates, 84 obese subjects underwent bariatric surgery and adipose Angptl4 expressions were analyzed. The adipose Angptl4 mRNA levels and protein abundances were correlated with FTO AA or AT haplotype. The magnitude of excess body weight reduction 2 years after bariatric surgery was correlated with the adipose ANGPTL4 protein levels. ConclusionAdipose ANGPTL4 abundances were affected by the presence of FTO obesity risk haplotype and correlated with excess weight loss percentage after bariatric surgery. These data signify the critical role of FTO variants and adipose ANGPTL4 in fatty acid metabolism and bariatric outcomes in humans.

Ancestry specific associations of FTO gene variant and metabolic syndrome

Cross-sectional studies indicate that the fat mass and obesity-associated (FTO) rs9939609 gene variant is associated with metabolic syndrome (MetS) primarily in European ancestry. However, the association is not fully elucidated in African Americans.We hypothesized that rs9939609 (AT = moderate-risk carriers or AA = high-risk carriers compared to TT = low-risk carriers) is associated with MetS and its component risk factors over time; and that its association is ancestry-specific. A secondary hypothesis was that higher levels of physical activity can decrease the deleterious effect of rs9939609 at higher body mass index (BMI).Atherosclerosis Risk in Communities study repeated measures data from 4 visits (1987–1998) were obtained from the database of Genotypes and Phenotypes for 10,358 participants (8170 Whites and 2188 African Americans) aged 45 to 64 years at baseline. Guidelines for elevated blood pressure by the American College of Cardiology and American Heart Association Task Force were updated within the MetS criteria. Risk ratios (RR) and 95% confidence intervals from generalized estimating equations assessed population-average risks.MetS was present among 3479 (42.6%) Whites and 1098 (50.2%) African Americans at baseline, and 50.3% Whites and 57% African Americans over 11-years of follow-up. Among MetS component risk factors, high waist circumference was most prevalent among White AT (RR = 1.07; 1.06–1.09) and AA (RR = 1.12; 1.10–1.14) higher-risk carriers. High triglycerides were elevated among African American AA high-risk carriers (RR = 1.11; 1.02–1.21) compared to TT low-risk carriers. Over time, White AT-and AA higher-risk carriers had 1.07 and 1.08-fold increase (P < .0001) in MetS risk. Physical activity had independent protective effects on MetS among both races (P < .05). White AA high-risk carriers with normal BMI and low vs high physical activity had higher MetS risk (RR = 1.69; 1.25–2.30 and RR = 0.68;0.53–0.87, respectively). In rs9939609 × BMI× physical activity interaction, White A-allele high-risk carriers had lower MetS risk (RR = 0.68; 0.53–0.87). Among Whites, physical activity can lessen the effect of rs9939609 and high BMI on risk for MetS.

Similarities in Metabolic Flexibility and Hunger Hormone Ghrelin Exist between FTO Gene Variants in Response to an Acute Dietary Challenge

The rs9939609 polymorphism of the fat mass and obesity-associated (FTO) gene has been associated with obesity, and studies have also shown that environmental/lifestyle interaction such as dietary intake might mediate this effect. The current study investigates the postprandial hormonal regulators of hunger and indirect markers of substrate utilisation and metabolic flexibility following a dietary challenge to determine if suppression of circulating ghrelin levels and/or reduced metabolic flexibility exist between FTO genotypes. One hundred and forty seven healthy, sedentary males and females (29.0 ± 0.7 yrs; 70.2 ± 1.1 kg; 169.1 ± 0.8 cm; 24.5 ± 0.3 kg/m2) complete a single experimental session. Anthropometric measures, circulating levels of active ghrelin, insulin and glucose, and substrate oxidation via indirect calorimetry, are measured pre-prandial and/or post-prandial. The FTO rs9939609 variant is genotyped using a real-time polymerase chain reaction. Metabolic flexibility (∆RER) is similar between FTO genotypes of the rs9939609 (T > A) polymorphism (p > 0.05). No differences in pre-prandial and/or postprandial substrate oxidation, plasma glucose, serum insulin or ghrelin are observed between genotypes (p > 0.05). These observations are independent of body mass index and gender. Altered postprandial responses in hunger hormones and metabolic flexibility may not be a mechanism by which FTO is associated with higher BMI and obesity in healthy, normal-weighted individuals.

Physical Activity Might Reduce the Adverse Impacts of the FTO Gene Variant rs3751812 on the Body Mass Index of Adults in Taiwan.

The fat mass and obesity-associated (FTO) gene is a significant genetic contributor to polygenic obesity. We investigated whether physical activity (PA) modulates the effect of FTO rs3751812 on body mass index (BMI) among Taiwanese adults. Analytic samples included 10,853 Taiwan biobank participants. Association of the single-nucleotide polymorphism (SNP) with BMI was assessed using linear regression models. Physical activity was defined as any kind of exercise lasting 30 min each session, at least three times a week. Participants with heterozygous (TG) and homozygous (TT) genotypes had higher BMI compared to those with wild-type (GG) genotypes. The β value was 0.381(p < 0.0001) for TG individuals and 0.684 (p = 0.0204) for TT individuals. There was a significant dose-response effect among carriers of different risk alleles (p trend <0.0001). Active individuals had lower BMI than their inactive counterparts (β = −0.389, p < 0.0001). Among the active individuals, significant associations were found only with the TG genotype (β = 0.360, p = 0.0032). Inactive individuals with TG and TT genotypes had increased levels of BMI compared to those with GG genotypes: Their β values were 0.381 (p = 0.0021) and 0.950 (p = 0.0188), respectively. There was an interaction between the three genotypes, physical inactivity, and BMI (p trend = 0.0002). Our data indicated that increased BMI owing to genetic susceptibility by FTO rs3751812 may be reduced by physical activity.

Adolescent obesity and the role of the fat mass and obesity-associated gene polymorphism.

The association between fat mass and obesity-associated (FTO) gene and obesity is unclear in both adults and adolescents. The aim of this study was to examine the role of the FTO gene variant rs9939609 as a candidate gene for obesity and the relationship between insulin resistance (IR), metabolic syndrome (MetS), estimated glomerular filtration rate (eGFR) and neutrophil-to-lymphocyte ratio (NLR). Obese adolescents (n=100) and healthy controls (n=100) were included. Rs9939609 polymorphism in the FTO gene was genotyped by PCR-SNaPshot. The prevalence of insulin resistance (IR), metabolic syndrome (MetS) and hyperfiltration were 47%, 60% and 27%, respectively. There were no significant differences in genotype and allele frequencies between obese adolescents and controls; however, prevalence of MetS in female patients with A allele carriers was more frequent and prevalence of hyperfiltration was less frequent with T allele carriers (P.

FTO gene polymorphisms (rs9939609 and rs17817449) as predictors of Type 2 Diabetes Mellitus in obese Iraqi population

BackgroundThe variation of the SNPs in FTO (fat mass and obesity associated) gene are improved to be associated with obesity and type 2 diabetes (T2DM) in some ethnic groups for example in European while, this consistency is controversial in Asians and there were few studies in Iraqi population about the effect of this gene on the development of T2DM in obese patients. Therefore, the objective of this study is to investigate the impact of the two common FTO gene variants in the development of T2DM in obese Iraqi patients. MethodsA case-control study in which the FTO gene variants rs9939609 and rs17817449 were genotyping in a total of 800 individuals, 400 T2DM obese patients (patients group) and 400 healthy control obese volunteers (control group) to explore the relation of these SNPs with T2DM in obese Iraqi population. The patients group was enrolled from diabetic clinic in Al Najaf al Ashraf based on WHO guidelines of T2DM. From whole blood the DNA was extraction and genotyped by using ScaI and AlwNI enzymes respectively in the PCR–RFLP technique. Multinomial logistic regression was applied to compare the proportions of genotypes and alleles. The odd's ratio, t-test P value at 95% confidence interval were measured before and after adjustment of BMI, age and sex adjustment. The genetic power, Hardy Weinberg equilibrium and haplotype analysis were tested in the present study. ResultsIt was observed that the presence of T allele in the two SNPs rs9939609 and rs17817449 in the FTO gene polymorphisms was associated with increased risk for the development of T2DM in Iraqi obese individuals. The minor allele (T) in rs9939609 was significantly higher (P=0.0001) in T2DM (31.25%) when compared with that of the control obese group (20%). The Homozygous genotype (TT) significantly (OR=3.25, CI 95% 1.87–5.64, P=0.000) increased the risk of T2DM by three folds with respect to those of wild type (AA) after adjustment for age, sex and BMI, furthermore, it was significantly increased the risk in the dominant, recessive and additive models (P=0.000,0.000 and 0.0001 respectively). The T allele in rs17817449 was also significantly higher (P=0.0001) in patients group (36.25%) when compared with that of the control group (27.25%). The Heterozygous genotype (TG) significantly (OR=2.24, CI 95% 1.65–3.04, P=0.000) increased the risk of T2DM more than two folds with respect to those of wild type (GG) after adjustment for age, sex and BMI, and it was significantly increased the risk in the dominant models (P=0.000). In the relation to the phenotypic parameters the two SNPs were significantly associated with increased BMI, LDL, insulin and HOMA-IR and a decrease the HDL levels. ConclusionThe FTO gene polymorphisms rs9939609 and rs17817449 play a role in the in the development of insulin resistance and hence occurrence of type 2 DM in obese patients.

FTO Gene Associates and Interacts with Obesity Risk, Physical Activity, Energy Intake, and Time Spent Sitting: Pilot Study in a Nigerian Population.

Fat mass and obesity-associated (FTO) gene influences obesity but studies have shown that environmental/lifestyle variables like physical activity (PA), time spent sitting (TSS), and energy intake might mediate the effect. However, this is poorly understood in Nigeria due to scarce studies. We demystified association and interaction between FTO rs9939609, obesity, PA, TSS, and energy intake in Nigeria. FTO gene variant was genotyped by restriction fragment length polymorphism and gene sequencing analysis in 103 people with obesity and 98 controls. Anthropometrics and environmental variables were measured using standard procedures. Significant associations were found between FTO rs9939609 with obesity and environmental/lifestyle variables before and after adjusting for age. Carriers of allele A have significantly higher odds of being overweight/obese using BMI [0.191 (0.102–0.361), p < 0.001] but this was attenuated by PA (p[interaction] = 0.029); odds of being overweight reduced from 0.625 (0.181–2.159) to 0.082 (0.009–0.736) for low and high PA, respectively. Mediation analysis of total indirect effect also confirmed this by showing a simultaneous mediating role of total PA, energy intake, and TSS in the relationship between FTO and BMI (unstandardized-coefficient = 1.68; 95% CI: 1.26–2.22). This study shows a relationship between FTO and obesity phenotype and environmental/lifestyle factors might be an important modulator/mediator in the association.

Association of Fat Mass and Obesity-associated Gene Variant with Lifestyle Factors and Body Fat in Indian Children.

Context:Common intronic variants of the fat mass and obesity-associated (FTO) gene have been associated with obesity-related traits in humans.Aims:(1) The aim of this study is to study the distribution of FTO gene variants across different body mass index (BMI) categories and (2) to explore the association between FTO gene variants and lifestyle factors in obese and normal weight Indian children.Subjects and Methods:Fifty-six children (26 boys, mean age 10.3 ± 2.2 years) were studied. Height, weight, and waist and hip circumference were measured. Physical activity (questionnaire) and food intake (food frequency questionnaire) were assessed. Body fat percentage (%BF) was measured by dual-energy X-ray absorptiometry. FTO allelic variants at rs9939609 site were detected by SYBR Green Amplification Refractory Mutation System real-time polymerase chain reaction using allele-specific primers. Generalized linear model was used to investigate the simultaneous influence of genetic and lifestyle factors on %BF.Results:Mean height, weight, and BMI of normal and obese children were 130.6 ± 7.1 versus 143.2 ± 15.6, 24.0 ± 5.2 versus 53.1 ± 15.8, and 13.9 ± 2.1 versus 25.3 ± 3.2, respectively. The frequency of AA allele was 57% among obese children and 35% in normal weight children. Children with the AA allele who were obese had least physical activity, whereas children with AT allele and obesity had the highest intake of calories when compared to children who had AT allele and were normal. %BF was positively associated with AA alleles and junk food intake and negatively with healthy food intake and moderate physical activity.Conclusions:Healthy lifestyle with high physical activity and diet low in calories and fat may help in modifying the risk imposed by FTO variants in children.

Genetic, dietary, and non-dietary risk factors of obesity among preparatory-year female students at Taibah University, Saudi Arabia

Genetic factors have a strong influence on obesity and are associated with body mass index (BMI). No study has investigated the relationships between glucose, the fat mass and obesity-associated (FTO) gene, obesity (BMI), and other metabolic-related traits in Saudi Arabia. This study was conducted to identify the association between glucose, BMI and the FTO rs9939609 variant with different metabolic traits among 186 female preparatory students at Taibah University in 2015. The subjects were divided into two categories based on glucose level and BMI. The results showed that 1/10th of the students were non-obese, while approximately 1/3rd had a high glucose level (HGL). The HGL group had higher mean levels of glucose, cholesterol, triglycerides, HDL, LDL, VLDL, and malondialdehyde compared to those of the normal glucose level (NGL) group. A highly positive correlation between glucose and some biochemical parameters was found in the HGL group (P<0.05), while no correlation was found between glucose and biochemical parameters, except for the cholesterol and triglyceride levels, in the NGL group. According to the t-test, none of the biochemical parameters were significant, and no correlation existed between these parameters and glucose, except for BMI. More than 90% of the students were not aware that they had an HGL or high cholesterol level according to their response to the questionnaire distributed at the beginning of this study. These problems mainly arose from the students’ diet, lack of exercise, and lifestyle. Of the 75% of students that had the T-allele, approximately 50% had the heterozygous FTO rs9939609 genotype AT. Genotypes were in Hardy–Weinberg equilibrium (P>0.05) in the whole population (n=186) in both obese and non-obese groups and both HGL and NGL groups. In conclusion, a positive correlation between glucose and some biochemical parameters was found in the HGL group; 24.5% of the population had the (A allele) risk factor, and 32% and 98% of the population were homozygous (AA) and heterozygous (AT) for the rs9939609 FTO obesity-risk allele that is responsible for greater energy intake. Future studies are required to study the FTO gene variant and its association with different biochemical parameters, mainly glucose, weight, and BMI, between males and females at different ages and locations in Saudi Arabia.

Interaction between FTO gene variants and lifestyle factors on metabolic traits in an Asian Indian population.

BackgroundLifestyle factors such as diet and physical activity have been shown to modify the association between fat mass and obesity–associated (FTO) gene variants and metabolic traits in several populations; however, there are no gene-lifestyle interaction studies, to date, among Asian Indians living in India. In this study, we examined whether dietary factors and physical activity modified the association between two FTO single nucleotide polymorphisms (rs8050136 and rs11076023) (SNPs) and obesity traits and type 2 diabetes (T2D).MethodsThe study included 734 unrelated T2D and 884 normal glucose-tolerant (NGT) participants randomly selected from the urban component of the Chennai Urban Rural Epidemiology Study (CURES). Dietary intakes were assessed using a validated interviewer administered semi-quantitative food frequency questionnaire (FFQ). Physical activity was based upon the self-report. Interaction analyses were performed by including the interaction terms in the linear/logistic regression model.ResultsThere was a significant interaction between SNP rs8050136 and carbohydrate intake (% energy) (Pinteraction = 0.04), where the ‘A’ allele carriers had 2.46 times increased risk of obesity than those with ‘CC’ genotype (P = 3.0 × 10−5) among individuals in the highest tertile of carbohydrate intake (% energy, 71 %). A significant interaction was also observed between SNP rs11076023 and dietary fibre intake (Pinteraction = 0.0008), where individuals with AA genotype who are in the 3rd tertile of dietary fibre intake had 1.62 cm lower waist circumference than those with ‘T’ allele carriers (P = 0.02). Furthermore, among those who were physically inactive, the ‘A’ allele carriers of the SNP rs8050136 had 1.89 times increased risk of obesity than those with ‘CC’ genotype (P = 4.0 × 10−5).ConclusionsThis is the first study to provide evidence for a gene-diet and gene-physical activity interaction on obesity and T2D in an Asian Indian population. Our findings suggest that the association between FTO SNPs and obesity might be influenced by carbohydrate and dietary fibre intake and physical inactivity. Further understanding of how FTO gene influences obesity and T2D through dietary and exercise interventions is warranted to advance the development of behavioral intervention and personalised lifestyle strategies, which could reduce the risk of metabolic diseases in this Asian Indian population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-016-0098-6) contains supplementary material, which is available to authorized users.

FTO gene variant modulates the neural correlates of visual food perception

Variations in the fat mass and obesity associated (FTO) gene are currently the strongest known genetic factor predisposing humans to non-monogenic obesity. Recent experiments have linked these variants to a broad spectrum of behavioural alterations, including food choice and substance abuse. Yet, the underlying neurobiological mechanisms by which these genetic variations influence body weight remain elusive.Here, we explore the brain structural substrate of the obesity-predisposing rs9939609 T/A variant of the FTO gene in non-obese subjects by means of multivariate classification and use fMRI to investigate genotype-specific differences in neural food-cue reactivity by analysing correlates of a visual food perception task. Our findings demonstrate that MRI-derived measures of morphology along middle and posterior fusiform gyrus (FFG) are highly predictive for FTO at-risk allele carriers, who also show enhanced neural responses elicited by food cues in the same posterior FFG area. In brief, these findings provide first-time evidence for FTO-specific differences in both brain structure and function already in non-obese individuals, thereby contributing to a mechanistic understanding of why FTO is a predisposing factor for obesity.

The Frequencies of Haplotypes of FTO Gene Variants and Their Association with the Distribution of Body Fat in Non-Obese Poles.

The minor allele frequencies (MAFs) of the FTO gene vary substantially among different ethnic groups, and this variation may explain, to some degree, the differences between estimates of the effects of these alleles on body fat distribution indicators. The aim of this study was to investigate the prevalence of fat mass and obesity associated (FTO) gene variants characterizing the structure of FTO haplotypes in a large Polish population, and to examine the influence of FTO gene variants on body fat distribution among metabolically obese normal weight (MONW) individuals, i.e. those with a normal BMI and visceral obesity. A total of 854 non-obese individuals aged from 20 to 40 years, residing in three different regions in Poland, were studied. All the patients from this group were genotyped for four FTO gene variants (rs9939609, rs9930506, rs1421085 and rs1121980). Simultaneous identification of all single nucleotide polymorphisms (SNPs) was conducted using the minisequencing method with a pair of designed specific primers. Over 90% of the diplotypes contain only the two most common haplotypes, in three combinations of haplotype pairs: CTAT/CTAT comprised 26.9% in women and 30.9% in men; CTAT/TCGA comprised 45.0% in women and 44.4% in men; and TCGA/TCGA comprised 19.3% in woman and 14.8% in men. The analysis of the variance in body fat distribution parameters shows no statistically significant differences between the three common haplotype pairs in either men or women. The young Polish population is characterized by two disparate haplotypes of common FTO gene variants: TCGA (a risk SNP haplotype), and CTAT (a protective haplotype). No significant differences were found between fat distribution indicators in relation to haplotypes in either women and men.

FTO gene variants are associated with growth and carcass traits in cattle.

An important aim in animal breeding is the improvement of growth and meat quality traits. Previous studies have demonstrated that genetic variants in the fat mass and obesity associated (FTO) gene have a relatively large effect on human obesity as well as on body composition in rodents and, more recently, in livestock. Here, we examined the effects of the FTO gene variants on growth and carcass traits in the Slovenian population of Simmental (SS) and Brown (SB) cattle. To validate and identify new polymorphisms, we used sequencing, PCR-RFLP analysis and TaqMan assays in the SS breed and FTO gene variants data from the Illumina BovineSNP50 v1 array for the SB breed. Sequencing of the eight samples of progeny-tested SS sires detected 108 single nucleotide polymorphisms (SNPs) in the bovine FTO gene. Statistical analyses between growth and carcass traits and 34 FTO polymorphisms revealed significant association of FTO variants with lean meat percentage in both breeds. Additionally, FTO SNPs analyzed in SS cattle were associated with fat percentage, bone weight and live weight at slaughter. The FTO gene can thus be regarded as a candidate gene for the marker-assisted selection programs in our and possibly other populations of cattle. Future studies in cattle might reveal novel roles for the FTO gene in shaping carcass traits in livestock species as well as body composition control in other mammals.

A single FTO gene variant rs9939609 is associated with body weight evolution in a multiethnic extremely obese population that underwent bariatric surgery

ObjectivesThe rs9939609 single nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene is involved in obesity. Few studies have been conducted on patients who underwent bariatric surgery. The aim of this study was to evaluate the influence of FTO SNPs on body weight, body composition, and weight regain during a 60-mo follow-up period after bariatric surgery. MethodsThe rs9939609 was genotyped in 146 individuals using a real-time polymerase chain reaction TaqMan assay. Data for lifestyle, comorbidities, body weight, body mass index (BMI), excess weight loss (EWL), and body composition were obtained before and 6, 12, 18, 24, 36, 48, and 60 mo after surgery. Data were analyzed by comparing two groups of patients according to rs9939609 FTO gene polymorphism. Mixed-regression models were constructed to evaluate the dynamics of body weight, BMI, and EWL over time in female patients. ResultsNo differences were observed between the groups during the first 24 mo after surgery. After 36, 48, and 60 mo, body weight, fat mass, and BMI were higher, whereas fat-free mass and EWL were lower in the FTO-SNP patient group. Weight regain was more frequent and occurred sooner in the FTO-SNP group. ConclusionsThere is a different evolution of weight loss in obese carriers of the FTO gene variant rs9939609 after bariatric surgery. However, this pattern was evident at only 2 y postbariatric surgery, inducing a lower proportion of surgery success and a greater and earlier weight regain.

Association of FTO Mutations with Risk and Survival of Breast Cancer in a Chinese Population.

Recently, several studies have reported associations between fat mass and obesity-associated (FTO) gene mutations and cancer susceptibility. But little is known about their association with risk and survival of breast cancer in Chinese population. The aim of this study is to examine whether cancer-related FTO polymorphisms are associated with risk and survival of breast cancer and BMI levels in controls in a Chinese population. We genotyped six FTO polymorphisms in a case-control study, including 537 breast cancer cases and 537 controls. FTO rs1477196 AA genotype had significant decreased breast cancer risk [odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.34–0.86] compared to GG genotype, and this association was only found in women with BMI < 24 kg/m2 (OR = 0.41, 95% CI: 0.22–0.76); and rs16953002 AA genotype conferred significant increased breast cancer risk (OR = 1.80, 95% CI: 1.23–2.63) compared to GG genotype. Haplotype analysis showed that FTO TAC haplotype (rs9939609-rs1477196-rs1121980) had significant reduced breast cancer risk (OR = 0.76, 95% CI: 0.62–0.93) compared with TGC haplotype. But we failed to find any association between FTO polymorphisms and breast cancer survival. These findings suggest that variants in FTO gene may influence breast cancer susceptibility.