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AbstractOur meta-analysis, encompassing 30 studies with 46,976 subjects, aimed to explore the impact of fat mass and obesity-associated protein (FTO) genotypes on weight response to exercise and dietary interventions in overweight and obese adults. Electronic databases including PubMed and Google Scholar were searched from 2020 to September 2023 to identify relevant studies. Results revealed a significant reduction in body weight among individuals with the FTO risk allele following exercise and diet interventions (standardized mean difference [SMD] = − 0.619, 95% CI: − 1.137, − 0.100; p = .01). When examining FTO variants, both AA (SMD = − 0.148, 95% CI: − 0.282, − 0.014, p = .03, I2 = 24.96) and TA genotypes (SMD = − 0.674, 95% CI: − 1.162, − 0.186, p = .007, I2 = 91.12) showed significant weight reduction compared to the TT genotype. Moreover, individuals with the high-risk genotype AA + TT achieved greater weight loss compared to those with the normal-risk genotype TT (SMD = − 0.419, 95% CI: − 0.655, −0.183, p = .0001, I2 = 92.08) in the dominant genetic model. Subgroup analysis indicated that FTO risk allele carriers (AA + AT) with exercise interventions lasting six months and a body mass index of 25 – 29 experienced greater weight loss compared to TT carriers. These findings emphasize the importance of genetic considerations in weight management interventions and suggest personalized approaches for combating obesity. Further clinical trials are warranted to validate our study’s findings. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the frequencies of alleles and genotypes of the single nucleotide polymorphism of the FTO gene (rs17817449) and the intensity of physical activity in relation to the BMI of subjects in the student population. Genotyping was performed using the PCR-RFLP method. 94 subjects stated that they were not physically active, 57 subjects were moderately physically active and 52 were intensely physically active. In the total sample, the risk allele G of the investigated polymorphism rs17817449 of the FTO gene had a lower frequency (41.8%) compared to the normal allele T (58.13%). Although a higher frequency of the risk allele G was found in the group of overweight subjects compared to the group with BMI < 25, the difference was not statistically significant (p > 0.05).

Introduction: FTO gene belongs to the non-heme Fe (II) and 2 oxoglutarate-dependent dioxygenase superfamily. Polymorphisms within the first intron of the FTO gene have been examined across various populations, yielding disparate findings.The present study aimed to determine the impact of two intronic polymorphisms FTO 30685T/G (rs17817449) and -23525T/ A (rs9939609) on the risk of obesity in Punjab, India. Methods: Genotypic and biochemical analysis were done for 671 unrelated participants (obese = 333 and non-obese = 338) (age ≥ 18 years). Genotyping of the polymorphisms was done by PCR-RFLP method. However, 50% of the samples were sequenced by Sanger sequencing. Results: Both the FTO variants 30685 (TT vs GG: odds ratio (OR), 2.30; 95% confidence interval (CI), 1.39-3.79) and -23525 (TT vs AA: odds ratio (OR), 2.78; 95% confidence interval (CI), 1.37-5.64) showed substantial risk towards obesity by conferring it 2 times and 3 times, respectively. The analysis by logistic regression showed a significant association for both the variants 30685T/G (rs17817449) and -23525T/A (rs9939609) (OR = 2.29; 95%CI: 1.47-3.57) and (OR = 5.25; 95% CI: 2.68-10.28) under the recessive genetic model, respectively. The haplotype combination TA (30685; -23525) develops a 4 times risk for obesity (P = 0.0001). Among obese, the G allele of 30685T/G and A- allele of -23525T/A showed variance in Body mass index (BMI), waist circumference (WC), waist-to-height ratio(WHtR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and triglyceride(TG). Conclusion: The present investigation indicated that both the FTO 30685T/G (rs17817449) and -23525T/A (rs9939609) polymorphisms have a key impact on an individual's vulnerability to obesity in this population. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the frequencies of alleles and genotypes of the single nucleotide polymorphism of the FTO gene (rs17817449) and the intensity of physical activity in relation to the BMI of subjects in the student population. Genotyping was performed using the PCR-RFLP method. 94 subjects stated that they were not physically active, 57 subjects were moderately physically active and 52 were intensely physically active. In the total sample, the risk allele G of the investigated polymorphism rs17817449 of the FTO gene had a lower frequency (41.8%) compared to the normal allele T (58.13%). Although a higher frequency of the risk allele G was found in the group of overweight subjects compared to the group with BMI < 25, the difference was not statistically significant (p > 0.05). [ABSTRACT FROM AUTHOR]

AIM: To investigate the influence of fat mass and obesity-associated（Fto) gene on the aberrant contraction of aortic smooth muscle in diabetes mellitus(DM) mice, and to explore the mechanism of Fto gene underlying the calcium regulation. METHODS: Smooth muscle-specific Fto gene knockout(FtoSMKO) mice were generated using CreloxP technology. The experiment involved 3 groups of mice: wild-type(WT) group, DM model group and FtoSMKO-DM group, with 15 mice in each group. In DM group and FtoSMKO-DM group, type 1 DM was induced by intraperitoneal injection of streptozotocin. The mice in WT group were injected with equal volume of citric acid-sodium citrate buffer solution. The influences of different drugs on the contraction responses of aortic smooth muscle in mice were analyzed using a multimyograph system. The expression level of FTO protein in the aortic tissues was detected by Western blot. RESULTS: (1) Compared with WT mice, the expression levels of FTO protein in the aortic tissues of DM mice were significantly increased(P<0. 01) .(2) The expression level of FTO protein in smooth muscle was significantly decreased after knockout of Fto gene(P<0. 01) . Compared with WT group, the mice in DM group exhibited a significant decrease in body weight and a marked increase in fasting blood glucose level(P<0. 05) . There were no noticeable differences in body weight or fasting blood glucose level between FtoSMKO-DM group and DM group(P>0. 05) .(3) The contraction responses of aortic smooth muscle in DM group were substantially increased by phenylephrine compared with WT group. Specifically, vasoconstriction responses mediated by non-L-type calcium channels and store-operated calcium channels (SOCC) were significantly enhanced in DM group. In addition, the responses mediated by inositol 1, 4, 5-trisphosphate receptors (IP3R), which facilitate calcium release from the sarcoplasmic reticulum, were significantly enhanced. However, the responses mediated by caffeine-activated ryanodine receptors(RyR), which also facilitate calcium release from the sarcoplasmic reticulum, were significantly inhibited(P<0. 05) .（4) Compared with DM group, the phenylephrine-induced contraction responses of aortic smooth muscle in FtoSMKO-DM group were greatly weakened(P<0. 05) . In particular, the vasoconstriction responses mediated by non-L-type calcium channels and SOCC in FtoSMKO-DM group were greatly suppressed (P<0. 05), while those mediated by caffeine-activated RyR were dramatically boosted(P<0. 05) . However, IP3R-mediated responses were not affected(P>0. 05) . CONCLUSION: Smooth muscle-specific Fto gene knockout suppresses contractile hyperre⁃ sponsiveness in the aortic smooth muscle of DM mice, which may be attributed to involvement of FTO protein in calcium regulation in the vascular smooth muscle. [ABSTRACT FROM AUTHOR]

Background: The FTO gene polymorphisms rs9939609 have been linked to obesity. It’s essential to note that genetic variations exist between different populations. This study aims to assess the correlation between FTO gene polymorphisms rs9939609 and the risk of obesity in adult populations from both Western and Asian countries. Methods: This research employed meta-analysis, conducting a comprehensive search across articles available in ProQuest, EBSCO, and PubMed from January 2013 to January 2024. Pooled Odds Ratio (POR) with 95 % CI were computed based on the collected data. Review Manager (RevMan) 5.4.1 and Stata 16.0 were employed for data analysis. Results: In Western compared to Asian countries, the FTO rs9939609 variant was found to be significantly associated with obesity in various genetic models: dominant (POR = 1.45 vs 1.45), recessive (POR = 1.33 vs 1.51), co-dominant (first model, POR = 1.56 vs 1.70; second model, POR = 1.30 vs 1.37), and allelic (POR = 1.61 vs 1.56) models. Moreover, in Western countries, the FTO rs9939609 variant’s association with obesity was homogeneous in the recessive and first co-dominant genetic models. In Asian countries, the association between FTO rs9939609 and obesity was homogeneous in the dominant, recessive, and co-dominant genetic models (I2

Abstract Background Single Nucleotide Polymorphisms (SNPs) of the Fat mass and obesity-associated (FTO) gene may be associated with obesity by regulating appetite. The present study aimed to investigate the relationship between FTO genotype and resistance to eating in male adolescents. Methods The present cross-sectional study included 246 adolescent boys in Tehran, Iran, who were assessed for self-efficacy related to weight control using the Weight Efficacy Lifestyle (WEL), questionnaire, food intake using the Food Frequency Questionnaire (FFQ), physical activity using the International Physical Activity Questionnaire (IPAQ), and anthropometric indices using Bio-Impedance Analyzer (BIA). Moreover, the participants underwent genotyping for the rs9930506 polymorphism of the FTO gene, and the relationship between FTO genotype and resistance to eating was investigated using different models of multiple linear regression. Results According to our findings, there was a significant reverse relationship between the FTO rs9930506 genotype and resistance to eating (β: -0.16, P = 0.01). Moreover, the relationship was still significant after adjusting for age, nutritional knowledge, BMI, and mother’s BMI, educational level, and occupational status. Conclusion According to our results, the FTO genotype had a significant effect on resistance to eating and food desires. However, there is a need for further studies to evaluate the underlying mechanisms of the effects of the FTO gene on appetite and obesity.

Abstract Background Polycystic ovary syndrome is a multifactorial endocrine disorder impacting women of reproductive age. Variations within the FTO gene have been linked to both obesity and type 2 diabetes mellitus. Given that PCOS is frequently associated with obesity and compromised glucose tolerance, we investigated the prevalence of the rs9939609 variant within the FTO gene among women diagnosed with PCOS and a control group. Our aim is to uncover potential correlations between this genetic variant, metabolic attributes, and endocrine markers within the Gujarat province of India. Method We enrolled a total of 114 participants, (62 individuals diagnosed with PCOS and 52 healthy controls). DNA extraction from venous blood was conducted for all participants. The rs9939609 polymorphism was investigated through tetra-primer amplification refractory mutation system-polymerase chain reaction. Furthermore, we performed biochemical assessments to quantify levels of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), total testosterone, prolactin (PRL), and Dehydroepiandrosterone sulfate (DHEAS). Statistical analyses were carried out utilizing SPSS version 21 (IBM, USA). Results The present study did not reveal any noteworthy association between cases and controls. The frequencies of genotypes and alleles within the cohorts displayed no statistically significant differences (p = 0.25, p = 0.68, and p = 0.78, respectively). The dominant model indicated a modest risk (OR:1.13, 95%CI: 0.55 to 2.38) toward PCOS development. There was a noticeable statistical difference observed in the levels of total testosterone, DHEAS, and BMI between the case and control groups (p

Fat mass and obesity-associated gene (FTO) is directly associated with increased risk of obesity and type 2 diabetes mellitus (T2DM). The purpose of current study was to investigate the effect of 12 weeks of resistance training (RT) on FTO expression in subcutaneous adipose tissue, glucose, and insulin levels in T2DM rats. Sixteen males Wistar rats (220±10 gr) with T2DM induced by streptozotocin-nicotinamide injection were randomly assigned into resistance training (RT; n=8) and control (Con; n=8) groups. RT was performed for 12 weeks, 5 days per week. FTO expression in subcutaneous adipose tissue, fasting blood glucose (FBS), insulin and insulin resistance (HOMA-IR) were measured 48 hours after the last exercise training session. After the exercise training intervention, the FTO expression (p=0.004) and FBS (p=0.001) were significantly lower in the RT compared to the Con group while the insulin in the RT was significantly higher than that in the Con group (p=0.001). There was no significant difference in the insulin resistance between the two groups (p˃0.05). According to findings, it seems that RT can decrease FBS and FTO expression in subcutaneous adipose tissue of T2DM rats. Improved blood glucose in diabetic rats might be partially attributed to reduced FTO expression in response to RT.

Background: Single Nucleotide Polymorphisms (SNPs) of the Fat mass and obesity-associated (FTO) gene may be associated with obesity by regulating appetite. The present study aimed to investigate the relationship between FTO genotype and resistance to eating in male adolescents. Methods: The present cross-sectional study included 246 adolescent boys in Tehran, Iran, who were assessed for self-efficacy related to weight control using the Weight Efficacy Lifestyle (WEL), questionnaire, food intake using the Food Frequency Questionnaire (FFQ), physical activity using the International Physical Activity Questionnaire (IPAQ), and anthropometric indices using Bio-Impedance Analyzer (BIA). Moreover, the participants underwent genotyping for the rs9930506 polymorphism of the FTO gene, and the relationship between FTO genotype and resistance to eating was investigated using different models of multiple linear regression. Results: According to our findings, there was a significant reverse relationship between the FTO rs9930506 genotype and resistance to eating (β: -0.16, P = 0.01). Moreover, the relationship was still significant after adjusting for age, nutritional knowledge, BMI, and mother’s BMI, educational level, and occupational status. Conclusion: According to our results, the FTO genotype had a significant effect on resistance to eating and food desires. However, there is a need for further studies to evaluate the underlying mechanisms of the effects of the FTO gene on appetite and obesity. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome is a multifactorial endocrine disorder impacting women of reproductive age. Variations within the FTO gene have been linked to both obesity and type 2 diabetes mellitus. Given that PCOS is frequently associated with obesity and compromised glucose tolerance, we investigated the prevalence of the rs9939609 variant within the FTO gene among women diagnosed with PCOS and a control group. Our aim is to uncover potential correlations between this genetic variant, metabolic attributes, and endocrine markers within the Gujarat province of India. Method: We enrolled a total of 114 participants, (62 individuals diagnosed with PCOS and 52 healthy controls). DNA extraction from venous blood was conducted for all participants. The rs9939609 polymorphism was investigated through tetra-primer amplification refractory mutation system-polymerase chain reaction. Furthermore, we performed biochemical assessments to quantify levels of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), total testosterone, prolactin (PRL), and Dehydroepiandrosterone sulfate (DHEAS). Statistical analyses were carried out utilizing SPSS version 21 (IBM, USA). Results: The present study did not reveal any noteworthy association between cases and controls. The frequencies of genotypes and alleles within the cohorts displayed no statistically significant differences (p = 0.25, p = 0.68, and p = 0.78, respectively). The dominant model indicated a modest risk (OR:1.13, 95%CI: 0.55 to 2.38) toward PCOS development. There was a noticeable statistical difference observed in the levels of total testosterone, DHEAS, and BMI between the case and control groups (p < 0.002, p < 0.0002, p < 0.0008). However, no variations in clinical variables were observed among genotypes within the PCOS group. Conclusion: This is the first study to investigate the association of FTO gene polymorphism and PCOS in Gujarati population. Our study findings indicate that the FTO gene variant is not directly linked to the onset of PCOS. However, it appears to exert an influence on metabolic factors such as obesity and insulin resistance. Notably, our results suggest that insulin resistance is more frequently observed among PCOS patients who are obese, as compared to those with non-obese PCOS patients. [ABSTRACT FROM AUTHOR]

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Background and Aims: Obesity is a growing public health concern in Bangladesh, which is influenced by a complex interplay of genetic and environmental factors. The genetic variant rs9939609 of the FTO (fat mass and obesity‐associated) gene has been found to be associated with an increased risk for obesity, depending on the population studied. The purpose of this cross‐sectional study is to examine the relationship between the FTO gene polymorphism (rs9939609) and lifestyle‐related risk factors, and their impact on obesity‐related traits and biochemical parameters in the Bangladeshi population. Methods: A total of 280 participants were enrolled in this study, comprising of 140 individuals with overweight and obesity (body mass index [BMI] ≥ 23.0) and 140 non‐overweight healthy individuals (18.5 ≤ BMI ≥ 22.9). Demographic information, dietary behaviors, and physical activity‐related data were collected using a structured questionnaire. Additionally, anthropometric assessments and measurements of biochemical parameters such as lipid profile and C‐reactive protein were performed. The amplification refractory mutation system‐polymerase chain reaction technique was used to identify single‐nucleotide polymorphism in the FTO gene. Descriptive statistics, χ,2 and one‐way ANOVA were performed to evaluate the relationships between independent and dependent variables. Results: The presence of rs9939609 was strongly associated with the obesity risk factors of increased BMI, cholesterol, triglycerides, and low‐density lipoprotein. We also found a significant association (p < 0.05) of rs9939609 with overweight and obesity in codominant AA versus TT (odds ratio [OR] = 0.299, 95% CI: 0.129−0.695) and AA versus AT (OR = 2.273, 95% CI: 1.023−5.053), recessive TT versus AA+AT (OR = 5.154, 95% CI: 2.463−10.782), and overdominant AT versus AA+TT (OR = 0.244, 95% CI: 0.122−0.488) models. Conclusion: FTO variant rs9939609 is significantly linked to obesity and an increased risk of hyperlipidemia in the Bangladeshi population. However, this association is intertwined with environmental factors such as diet and physical activity. [ABSTRACT FROM AUTHOR]

In this study, we aimed to estimate the association between the rs9939609 FTO (fat mass and obesity associated) polymorphism and a risk of overweight in children living in the Baikal region. We performed a case – control study that included 113 schoolchildren living in industrial centers of the Baikal region (Irkutsk, Angarsk, and Ulan-Ude). Anthropometric parameters were measured and body mass index was calculated with its values being ranked in accordance with the WHO BMI curves depending on a sex and age. Genotyping of the rs9939609 FTO polymorphism was performed by allele-specific amplification with real-time results detection. To assess likelihood of an association between the FTO gene allele and overweight and obesity, relative risk (RR) and 95 % confidence interval (CI) were calculated. The assessment revealed the A allele of the rs9939609 FTO polymorphism to be by 1.29 times more frequent in the examined children with overweight and obesity (48.44 %) than in the children form the reference group (37.65 %). The FTO rs9939609 polymorphism was authentically associated with likelihood of elevated risks of overweight and obesity in children with the homozygous AA genotype (RR = 2.806, 95 % CI: 1.650–4.772; STD = 0.271). Our study confirms that the rs9939609 polymorphism of the FTO gene is a risk factor of overweight and obesity for children from the Baikal region who have the A allele of the homozygous AA genotype. Prevailing frequency of the TT genotype (29.2 %) as compared with the AA genotype (10.62) is likely due to influence of assimilation processes on urbanized territories in the Baikal region.

Abstract Background Diabetes mellitus (DM) is a well-established determinant of atherosclerosis and cardiovascular diseases (CVD). Recently, genome-wide association studies (GWAS) identified several single nucleotide polymorphism (SNP) significantly correlated with DM. The study aimed to explore the relationships of the top significant DM SNPs with carotid atherosclerosis (CA). Methods We used a case–control design and randomly selected 309 cases and 439 controls with and without, respectively, carotid plaque (CP) from a community-based cohort. Eight recent GWAS on DM in East Asians reported hundreds of SNPs with genome-wide significance. The study used the top significant DM SNPs, with a p-value

In this review, we summarize the current state of knowledge on the fat mass and obesity-associated (FTO) gene and its role in obesity. The FTO-encoded protein is involved in multiple molecular pathways contributing to obesity as well as other metabolic complexities. This review emphasizes the epigenetic influence on the FTO gene as a new approach in the treatment and management of obesity. Several known substances have a positive effect on reducing FTO expression. Depending on which variant of the single nucleotide polymorphism (SNP) is present, the profile and level of gene expression changes. Implementation of environmental change measures could lead to reduced phenotypic manifestation of FTO expression. Treating obesity through FTO gene regulation will have to include various complex signal pathways in which FTO takes part. Identification of FTO gene polymorphisms may be useful for the development of individual obesity management strategies, including the recommendation of taking certain foods and supplements.

Abstract Background and Aims Obesity is a growing public health concern in Bangladesh, which is influenced by a complex interplay of genetic and environmental factors. The genetic variant rs9939609 of the FTO (fat mass and obesity‐associated) gene has been found to be associated with an increased risk for obesity, depending on the population studied. The purpose of this cross‐sectional study is to examine the relationship between the FTO gene polymorphism (rs9939609) and lifestyle‐related risk factors, and their impact on obesity‐related traits and biochemical parameters in the Bangladeshi population. Methods A total of 280 participants were enrolled in this study, comprising of 140 individuals with overweight and obesity (body mass index [BMI] ≥ 23.0) and 140 non‐overweight healthy individuals (18.5 ≤ BMI ≥ 22.9). Demographic information, dietary behaviors, and physical activity‐related data were collected using a structured questionnaire. Additionally, anthropometric assessments and measurements of biochemical parameters such as lipid profile and C‐reactive protein were performed. The amplification refractory mutation system‐polymerase chain reaction technique was used to identify single‐nucleotide polymorphism in the FTO gene. Descriptive statistics, χ,2 and one‐way ANOVA were performed to evaluate the relationships between independent and dependent variables. Results The presence of rs9939609 was strongly associated with the obesity risk factors of increased BMI, cholesterol, triglycerides, and low‐density lipoprotein. We also found a significant association (p

BackgroundFTO gene is associated with obesity, dietary intake, and the risk of colorectal cancer (CRC). In this study, patients with colorectal cancer were assessed for the interactions between FTO gene polymorphisms and dietary intake.MethodsThis case–control study was carried out on 450 participants aged 35–70 years including 150 patients with colorectal cancer and 300 healthy controls. Blood samples were collected in order to extract DNA and genotyping of FTO gene for rs9939609 polymorphism. A validated 168-item food frequency questionnaire (FFQ) and the Nutritionist-IV software were used to assess dietary intake.ResultsIn the participants with the TT genotype of FTO rs9939609 polymorphism, CRC risk was significantly associated with higher intake of dietary fat (OR:1.87 CI95%:1.76–1.99, p = 0.04), vitamin B3 (OR:1.20 CI95%:1.08–1.65, p = 0.04), and vitamin C (OR:1.06 CI95%:1.03–1.15, p = 0.04) and lower intake of β-carotene (OR:0.98 CI95%:0.97–0.99, p = 0.03), vitamin E (OR:0.77 CI95%:0.62–0.95, p = 0.02), vitamin B1 (OR:0.15 CI95%:0.04–0.50, p

Background: Diabetes mellitus (DM) is a well-established determinant of atherosclerosis and cardiovascular diseases (CVD). Recently, genome-wide association studies (GWAS) identified several single nucleotide polymorphism (SNP) significantly correlated with DM. The study aimed to explore the relationships of the top significant DM SNPs with carotid atherosclerosis (CA). Methods: We used a case–control design and randomly selected 309 cases and 439 controls with and without, respectively, carotid plaque (CP) from a community-based cohort. Eight recent GWAS on DM in East Asians reported hundreds of SNPs with genome-wide significance. The study used the top significant DM SNPs, with a p-value < 10–16, as the candidate genetic markers of CA. The independent effects of these DM SNPs on CA were assessed by multivariable logistic regression analyses to control the effects of conventional cardio-metabolic risk factors. Results: Multivariable analyses showed that, 9 SNPs, including rs4712524, rs1150777, rs10842993, rs2858980, rs9583907, rs1077476, rs7180016, rs4383154, and rs9937354, showed promising associations with the presence of carotid plaque (CP). Among them, rs9937354, rs10842993, rs7180016, and rs4383154 showed significantly independent effects. The means (SD) of the 9-locus genetic risk score (9-GRS) of CP-positive and -negative subjects were 9.19 (1.53) and 8.62 (1.63), respectively (p < 0.001). The corresponding values of 4-locus GRS (4-GRS) were 4.02 (0.81) and. 3.78 (0.92), respectively (p < 0.001). The multivariable-adjusted odds ratio of having CP for per 1.0 increase in 9-GRS and 4-GRS were 1.30 (95% CI 1.18–1.44; p = 4.7 × 10–7) and 1.47 (95% CI 1.74–9.40; p = 6.1 × 10–5), respectively. The means of multi-locus GRSs of DM patients were similar to those of CP-positive subjects and higher than those of CP-negative or DM-negative subjects. Conclusions: We identified 9 DM SNPs showing promising associations with CP. The multi-locus GRSs may be used as biomarkers for the identification and prediction of high-risks subjects for atherosclerosis and atherosclerotic diseases. Future studies on these specific SNPs and their associated genes may provide valuable information for the preventions of DM and atherosclerosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of different physical exercise programs and polymorphisms of the FTO (fat mass and obesity-associated gene) on body composition and cardiovascular risk factors in adolescents with overweight and obesity. Methods: A randomized, parallel, double-blind clinical trial consisting of the adolescent overweight from the state public network, in a simple representative random sample, who participated in an aerobic exercise or weight training intervention for 10 weeks. Anthropometry, body composition, biochemical markers, sexual maturation, and rs9939609 polymorphism in the FTO gene were assessed. 347 adolescents had their characterization of nutritional status. 72 individuals with overweight and obesity were invited to participate. 39 remained for the start of the program and were randomly allocated to both types of intervention. In the end, 26 subjects participated in the intervention programs, with 12 and 14 in the aerobic and weight training programs, respectively. Results: Heterozygous and homozygous bearers of risk allele A participating in the aerobic program showed improvements in glycemia (p = 0.002) and total cholesterol (p = 0.023) and a reduction in body fat mass (p = 0.041). The weight training program reduced glycemia in patients with the risk allele A (p = 0.027). Cameron's stage four sexual maturation participants were 2.1 times more likely to improve their body fat (CI = 1.31-3.39). Conclusion: Aerobic exercises produced exclusively a significant decrease in fat mass and total cholesterol in patients with risk allele A. Distinct physical exercise programs may cause diverse changes in risk variables related to the health of adolescents. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) regulates fat development in many ways. Low intramuscular fat (IMF) in rabbit meat seriously affects consumption. In order to improve meat quality, we explored the law of IMF deposition. FTO could increase the expression of APMAP and adipocyte differentiation through methylation. However, interference YTHDF2 can partially recover the influence of interference FTO on the APMAP gene and adipocyte differentiation. APMAP promoted the differentiation of adipocytes. Analysis of IMF and APMAP expression showed IMF content is positive with the expression level of the APMAP gene (p < 0.01). Conclusion: Together, FTO can regulate intramuscular fat by targeting the APMAP gene via an m6A-YTHDF2-dependent manner in Rex rabbits. The result provides a theoretical basis for the molecular breeding of rabbits. [ABSTRACT FROM AUTHOR]

(1) Background: obesity is a global public health problem; various factors have been associated with this disease, and genetic factors play a very important role. Previous studies in multiple populations have associated a gene with fat mass and obesity (FTO). Thus, the present work aims to identify and determine associations between genetic variants of FTO with indicators of overweight and obesity in the Mexican population. (2) Methods: a total of 638 subjects were evaluated to compile data on body mass index (BMI), the percentage of body fat (%BF), the waist circumference (WC), the serum levels of triglycerides (TG), and food consumption. A total of 175 genetic variants in the FTO gene were sampled by a microarray in the evaluated population, followed by association statistical analyses and comparisons of means. (3) Results: a total of 34 genetic variants were associated with any of the 6 indicators of overweight and obesity, but only 15 showed mean differences using the recessive model after the Bonferroni correction. The present study shows a wide evaluation of FTO genetic variants associated with a classic indicator of overweight and obesity, which highlights the importance of genetic analyses in the study of obesity. [ABSTRACT FROM AUTHOR]

In this review, we summarize the current state of knowledge on the fat mass and obesity-associated (FTO) gene and its role in obesity. The FTO-encoded protein is involved in multiple molecular pathways contributing to obesity as well as other metabolic complexities. This review emphasizes the epigenetic influence on the FTO gene as a new approach in the treatment and management of obesity. Several known substances have a positive effect on reducing FTO expression. Depending on which variant of the single nucleotide polymorphism (SNP) is present, the profile and level of gene expression changes. Implementation of environmental change measures could lead to reduced phenotypic manifestation of FTO expression. Treating obesity through FTO gene regulation will have to include various complex signal pathways in which FTO takes part. Identification of FTO gene polymorphisms may be useful for the development of individual obesity management strategies, including the recommendation of taking certain foods and supplements. [ABSTRACT FROM AUTHOR]

Abstract Background Polycystic ovary syndrome (PCOS) is a common endocrine–metabolic disorder due to genetic and environmental factors. Genetic variants located in intron 1 of Fat mass and obesity-associated (FTO) gene are associated with increased risk of obesity and metabolic disorders. This study aims to investigate the association of common FTO polymorphism rs9939609 in South Indian women with PCOS to assess its association with metabolic and endocrine parameters. FTO genotyping was done on 100 PCOS patients and 70 controls by Sanger sequencing. Results The distribution of rs9939609 was observed between groups (28% TT, 57% TA, and 15% AA for PCOS and 37.1% TT, 51.4% TA, and 11.4% AA for the controls). In the PCOS group, across the carriers of different genotypes, a significant association was found between body mass index (BMI), fasting glucose levels, and testosterone with the presence of at least one risk allele of FTO rs9939609. Logistic regression analysis showed the association of fasting glucose levels and testosterone (OR 1.30 [1.03–1.63] and OR 5.83 [1.61–21.11], respectively) with FTO rs9939609. Conclusions Our findings indicated that FTO SNP rs9939609 was not associated with PCOS, but suggested a significant association of rs9939609 with hyperandrogenemia, fasting glucose levels, and BMI in South Indian women with PCOS.

The purpose of the study was to investigate the association of carriage of rs9939609 polymorphism in the FTO gene with features of androgen status in men.Material and methods. The observational one-stage examination of 139 male patients aged 22 to 69 years, admitted to a therapeutic hospital in a planned manner has been carried out in the Clinic of the Federal Research Center for Fundamental and Translational Medicine in the period 2020–2021. All fasting men in the morning (8:00–8:30) were carried out of an anthropometric examination to determine physical development, sampling of venous blood from the cubital vein to assess the hormonal parameters of androgen status, and taking a sample of the buccal epithelium for molecular genetic research. Based on the carriage of the rs9939609 (T>A) polymorphism of the FTO gene, the following groups (G) of patients were distinguished: G1 – wild-type homozygotes (WT/WT), G2 – heterozygotes (WT/A), G3 – homozygotes for the mutant allele (A/A).Results and discussion. The statistically significant differences were found in the levels of total testosterone between G1 and G3 (11.6 vs 14.5 nmol/L, p = 0.010), as well as free testosterone in G1 compared to G2 (0.233 vs 0.287 nmol/L, p = 0.012) and G3 (0.233 vs 0.321 nmol/L, p = 0.002) when analyzing the clinical-anthropometric and hormonal features of the androgen status of the examined male patients in the selected groups. Assessment of the association revealed statistically significant positive correlations between the carriage of the mutant allele and the levels of total (r = 0.247; p = 0.013) and free (r = 0.296; p = 0.003) testosterone, and negative - with the frequency of androgen deficiency according to the free testosterone criteria (r = –0.240; p = 0.016).Conclusions. It has been shown that the carriage of the A/A genotype of rs9939609 polymorphism of the FTO gene is associated with an increase in the levels of total and free testosterone, that indicates a protective effect against the development of androgen deficiency in men. The obtained results suggest that this effect is due to the epigenetic effect of the FTO gene protein product on the expression of other genes involved in the synthesis of androgens in the gonads, but also in the adrenal cortex since no association of the carriage of the rs9939609 polymorphism of the FTO gene with the DHEA-C level was found.

OBJECTIVE: One genetic variant (rs1121980) of FTO gene has been related with body mass index and visceral adiposity. The objective of our study was to investigate the role of rs1121980 genetic variant of FTO gene on weight loss and metabolic changes secondary to a partial meal replacement (pMR) hypocaloric diet. PATIENTS AND METHODS: We conducted an interventional study on 219 obese Caucasian subjects with body mass index (BMI) > 30 kg/ m2. The subjects received two intakes per day of a normocaloric hyperproteic formula for 12 weeks. Adiposity and biochemical parameters (lipid profile, insulin, homeostasis model assessment (HOMA-IR) and glucose) were determined. RESULTS: After the pMR diet, body weight, BMI, fat mass, waist circumference, blood pressure, total-cholesterol, LDL-cholesterol, triglyceride, fasting insulin levels and HOMA-IR decreased in both genotype groups. The improvements in adiposity parameters and some biochemical parameters (insulin, HOMA-IR, triglyceride levels) were bigger in non-T allele carriers than in T allele carriers. The percentage of patients who achieved 7.5% weight loss was higher in the non-T carriers (76.7% vs. 48.4%), also with a different average of weight loss (-12.3±0.3 kg vs. -5.9±0.5 kg: p=0.01). The odds ratio to achieve 7.5% of weight loss was (OR= 2.22, 95% CI=1.24-4.01; p=0.02). CONCLUSIONS: Non-T allele carriers of rs1121980 show a higher magnitude of weight loss and improvement in adiposity parameters, insulin, HOMA-IR and triglyceride levels resulting from a pMR diet than T allele carriers. [ABSTRACT FROM AUTHOR]

OBJECTIVE: One genetic variant (rs1121980) of FTO gene has been related with body mass index and visceral adiposity. The objective of our study was to investigate the role of rs1121980 genetic variant of FTO gene on weight loss and metabolic changes secondary to a partial meal replacement (pMR) hypocaloric diet. PATIENTS AND METHODS: We conducted an interventional study on 219 obese Caucasian subjects with body mass index (BMI) > 30 kg/ m2. The subjects received two intakes per day of a normocaloric hyperproteic formula for 12 weeks. Adiposity and biochemical parameters (lipid profile, insulin, homeostasis model assessment (HOMA-IR) and glucose) were determined. RESULTS: After the pMR diet, body weight, BMI, fat mass, waist circumference, blood pressure, total-cholesterol, LDL-cholesterol, triglyceride, fasting insulin levels and HOMA-IR decreased in both genotype groups. The improvements in adiposity parameters and some biochemical parameters (insulin, HOMA-IR, triglyceride levels) were bigger in non-T allele carriers than in T allele carriers. The percentage of patients who achieved 7.5% weight loss was higher in the non-T carriers (76.7% vs. 48.4%), also with a different average of weight loss (-12.3±0.3 kg vs. -5.9±0.5 kg: p=0.01). The odds ratio to achieve 7.5% of weight loss was (OR= 2.22, 95% CI=1.24-4.01; p=0.02). CONCLUSIONS: Non-T allele carriers of rs1121980 show a higher magnitude of weight loss and improvement in adiposity parameters, insulin, HOMA-IR and triglyceride levels resulting from a pMR diet than T allele carriers. [ABSTRACT FROM AUTHOR]

Abstract Background FTO gene is considered to play an important role in many metabolic diseases. Evidence from studies indicated the possible association between the FTO rs9939609 polymorphisms with serum lipid profile. Therefore, this study aimed to investigate the association of FTO rs9939609 polymorphism with lipid profile in Iranian women. Methods This cross-sectional study was carried out on 380 adult women. Information about age, height, weight, BMI, physical activity, and dietary intake were collected. The serum levels of Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Triglyceride (TG), and total cholesterol were measured. The FTO gene was genotyped for rs9939609 polymorphism. The participants were divided into two groups of TT and AT/AA considering dominant model of FTO rs9939609 polymorphism. Results General characteristics of the participants with different FTO genotypes were not significantly different. The lower levels of HDL were observed in AT/AA genotypes compared to the TT wild type genotype of FTO rs9939609 polymorphism (P = 0.004). Adjustments of age, BMI, and physical activity did not change the results. Conclusions However, the significant association between FTO genotype and the HDL level was disappeared after further adjustments for dietary intake. Further studies are warranted to identify the underlying mechanisms of the possible association between FTO gene and serum lipid profile.

BackgroundGene polymorphisms may explain the controversy on the association between colorectal cancer (CRC) and dietary fibers. The purpose of this study was to investigate the effect of fat mass and obesity-associated (FTO) rs9939609 polymorphism on the association between colorectal cancer and dietary fiber.MethodsThis case-control study was conducted on 160 CRC cases and 320 healthy controls in Tehran, Iran. The participants' food intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). The frequency of rs9939609 FTO polymorphism in the case and control groups was determined using the tetra-primer amplification refractory mutation (tetra-ARMS) method.ResultsIn the participants with the TT genotype of the FTO rs9939609, the cases had higher BMI and lower intake of dietary fiber compared to the controls (P = 0.01). Among A allele carriers of FTO rs9939609 polymorphism, the cases had higher BMI (P = 0.04) and lower intake of total fiber (P = 0.02) and soluble fiber (P = 0.02). An inverse association was found between CRC and dietary fiber intake among those with the AA/AT FTO rs9939609 genotype after adjusting for age, sex, smoking, alcohol consumption, physical activity, BMI, and calorie intake (OR = 0.9, CI 95%:0.84–0.92, P < 0.05).ConclusionThis study found a link between higher dietary fiber consumption and a lower risk of CRC in A-allele carriers of FTO rs9939609 polymorphism. Future studies are needed to identify the underlying mechanisms of the association between CRC and dietary fibers in people with different FTO genotypes.

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Background: The role of the common FTO gene variant rs9939609 in obesity has been well established, and the FTO gene has a strong association with T2DM. Objective: To investigate the association of FTO gene variant rs9939609 with obesity-related parameters in T2DM and CVD patients. Materials and Methods: In this cross-sectional study, 280 subjects of either sex aged 45.10 ± 9.6 years were randomly divided into four groups, that is, T2DM, T2DM with CVD, nondiabetic with CVD disease, and normal control. These samples were genotyped by ARMS-PCR. The FTO gene association with obesity-related parameters in T2DM and CVD patients was analyzed by SPSS 22. Results: The TT genotype was the most common genotype (46.80%) in our study groups. The minor allele frequency (MAF) was significantly higher in T2DM patients (0.39 vs. 0.28), T2DM patients with CVD (0.43 vs. 0.28), and nondiabetic patients with CVD (0.35 vs. 0.28) as compared to control with p < 0.005. Carriers of the AA genotype of the FTO gene rs9939609 were significantly associated with increased BMI, WC, HbA1C, SBP, DBP, and TGs and lowered HDL cholesterol as compared to the TA and TT genotypes in T2DM and CVD patients with p < 0.005. The FTO gene variant rs9939609 showed a significant association with T2DM and CVD. The AA genotype odds ratio (OR) in T2DM was 1.48 (1.06-2.32), p = 0.006, and in CVD, it was 1.56 (1.04-2.4), p = 0.003. Conclusion: The FTO gene variant rs9939609 has a strong association with T2DM and CVD. The AA genotype of FTO gene variants rs9939609 showed a strong association with most of the risk factors of CVD and T2DM., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Mazhar Hussain et al.)

Background/Aim: Diabetes Mellitus (DM) is one of the important public health issues worldwide. The Fat mass obesity (FTO) gene rs-9939609 variant identified single nucleotide polymorphism (SNP) with the T to A missense mutation, and has a strong association with T2DM. FTO gene is present on chromosome “16q12.2” comprising of nine exons. FTO gene rs-9939609 a variant is commonly found in the Pakistani Population. The purpose of the study was to alert the population about the rs-9939609 variant SNP, having a strong association with T2DM. Material and Methods: Total of 190 participants were included in the present cross-sectional study. To collect the samples non-probability convenience technique was used. subjects were recruited and divided into three groups, normal healthy subjects, obese and T2DM. The patients were selected from the Medicine department Jamshoro/Hyderabad by filling the pre-designed proforma, as well as verbal and written consent taken from study participants. To analysed the data ANOVA Post hoc (Tukey-test) was applied for comparison among groups (P

Abstract Background The roles of FTO gene and the level of serum 25-OH-vitamin D in obesity are frequently reported. This study aimed to investigate the interactions of serum 25-OH-vitamin D level, FTO and IRX3 genes expression, and FTO genotype in obese and overweight boys. Methods This study was carried out on the 120 male adolescents with overweight in Tehran, Iran. Blood samples were collected from the participants in order to evaluate the serum level of 25-OH-vitamin D, the expression level of FTO and IRX3 genes, and FTO genotype for rs9930506 at baseline and after 18 weeks of the study. Results In general, no significant association was found between serum 25-OH-vitamin D level and IRX3 and FTO genes expression. The results of linear regression on the relationship between 25-OH-vitamin D serum level and FTO and IRX3 genes expression based on FTO genotypes for rs9930506 indicated that in AA/AG genotype carriers, serum 25-OH-vitamin D level was positively associated with FTO gene expression (B = 0.07, p = 0.02) and inversely associated with IRX3 gene expression (B = − 0.07, p = 0.03). In GG carriers, serum 25-OH-vitamin D level was not associated with expression of IRX3 and FTO genes. Conclusion There are significant interactions between 25-OH-vitamin D and the expression of FTO and IRX3 genes in the subset of obese patients with specific genotypes for FTO rs9930506. There was no association between serum 25-OH-vitamin D levels and the expression of FTO and IRX genes in individuals with a homozygous genotype for the risk allele of the FTO gene polymorphism.

Background and AimsWeight management is recommended in overweight or obese breast cancer patients, as they have an increased risk of cancer recurrence and poor prognosis. Furthermore, identifying the relationships between genetic factors and nutrition could help suggest possible individualized nutritional solutions in weight management. The objective of this pilot randomized controlled trial was to investigate the influence of two obesity-associated single nucleotide polymorphisms and the Mediterranean diet intervention on weight loss and modification of nutrient intake and metabolic parameters in overweight or obese, postmenopausal, breast cancer patients receiving adjuvant hormone therapy.MethodsSeventy-eight breast cancer patients were randomly assigned to the Mediterranean diet (MeDiet) group or control group, and seventy-one were finally analyzed. Body composition, nutrient intake, and metabolic parameters were assessed at baseline and after the 8-week intervention. Fat mass and obesity-associated (FTO) rs7185735 and melanocortin-4 receptor (MC4R) rs476828 variants were genotyped.ResultsWe found that both variants did not influence weight loss or improvement of metabolic parameters within the Mediterranean diet intervention. Intake of saturated fatty acid (SFA) and trans fat was significantly increased in C carriers compared with the TT genotype of MC4R rs476828 only in the control group (p = 0.002 for SFA; p = 0.016 for trans fat), whereas no significant difference was observed between genotypes in the MeDiet group. There were statistically significant interactions between MC4R rs476828 and dietary intervention for changes in SFA intake (p = 0.009) and trans fat intake (p = 0.049).ConclusionOur data suggest that considering the effects of genotype may be more necessary when the Mediterranean diet is not followed and that this diet may have a protective role against the effects of certain genotypes. Further studies are required to determine the potential mechanism of the observed gene-diet interaction.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT04045392].

Background. Genome-wide association studies have identified the alpha-ketoglutarate dependent dioxygenase gene (FTO) as the first susceptibility gene of obesity. In the present study, we utilized targeted metabolomics in an attempt to further elucidate mechanisms underlying the action of the FTO gene. Methods. This study was part of a health survey of employees of the Electricity Generating Authority of Thailand (n = 79, 10 female and 69 male). Targeted metabolomics was performed by liquid chromatography-mass spectrometry using Biocrates AbsoluteIDQ-p180 kit. Genotyping of FTO rs9939609 was performed by real-time PCR (TaqManTM MGB probes). Results. Using OPLS-DA variable importance in projection (VIP), tryptophan was found to be among the metabolites with the 10 highest VIP scores. Pearson's correlation analysis showed that kynurenine and tryptophan were positively correlated only in subjects with the rs9939609 A allele (n = 32, r = 0.56, p < 0.001) and the correlation coefficients were significantly higher in subjects having theA allele than in those without the A allele (p < 0.05). Moreover, the kynurenine/tryptophan ratio was significantly associated with the presence of the A allele, independently of body mass index and sex. Conclusions. The FTO gene is likely to influences the conversion of tryptophan to kynurenine. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a common endocrine–metabolic disorder due to genetic and environmental factors. Genetic variants located in intron 1 of Fat mass and obesity-associated (FTO) gene are associated with increased risk of obesity and metabolic disorders. This study aims to investigate the association of common FTO polymorphism rs9939609 in South Indian women with PCOS to assess its association with metabolic and endocrine parameters. FTO genotyping was done on 100 PCOS patients and 70 controls by Sanger sequencing. Results: The distribution of rs9939609 was observed between groups (28% TT, 57% TA, and 15% AA for PCOS and 37.1% TT, 51.4% TA, and 11.4% AA for the controls). In the PCOS group, across the carriers of different genotypes, a significant association was found between body mass index (BMI), fasting glucose levels, and testosterone with the presence of at least one risk allele of FTO rs9939609. Logistic regression analysis showed the association of fasting glucose levels and testosterone (OR 1.30 [1.03–1.63] and OR 5.83 [1.61–21.11], respectively) with FTO rs9939609. Conclusions: Our findings indicated that FTO SNP rs9939609 was not associated with PCOS, but suggested a significant association of rs9939609 with hyperandrogenemia, fasting glucose levels, and BMI in South Indian women with PCOS. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the contribution of the FTO A/T polymorphism (rs9939609) to the prediction of the future type 2 diabetes (T2D). A population-based prospective study included 1443 nondiabetic subjects at baseline, and they were examined for developing T2D after 5-year follow-up. Cox proportional hazards model was used to evaluate the hazard ratio (HR) of rs9939609 to the future T2D in the models adjusted for the confounding factors including socio-economic status, lifestyle factors (smoking and drinking history, sporting habits, and leisure time), and clinical patterns (obese status, blood pressures, and dyslipidemia) at baseline. The area under receiver operating characteristic curve (AUC) was used to measure the power to predict individuals with T2D. The FTO-rs9939609 polymorphism was a significant predictor of future T2D in the model unadjusted, and it remained significant in the final model after adjustment for the confounding factors, showing an additive effect of the A-allele (HR = 1.35, 95% CI = 1.02–1.78, P = 0.036, AUC = 0.676). For normoglycemic subjects at baseline, the similar final adjusted model reported the increased HR per A-allele (HR = 1.50, 95% CI = 1.09–2.07, P = 0.012, AUC = 0.697). Five-year changes in BMI, waist circumference, and systolic blood pressure did not remove the contribution of rs9939609 to increased HR of T2D. The population attributable risk for risk genotype was 13.6%. In conclusion, the study indicates that the FTO-rs9939609 polymorphism is an important genetic predictor for future T2D in Vietnamese population. [ABSTRACT FROM AUTHOR]

Background Genome-wide association studies have identified the alpha-ketoglutarate dependent dioxygenase gene (FTO) as the first susceptibility gene of obesity. In the present study, we utilized targeted metabolomics in an attempt to further elucidate mechanisms underlying the action of the FTO gene. Methods This study was part of a health survey of employees of the Electricity Generating Authority of Thailand (n = 79, 10 female and 69 male). Targeted metabolomics was performed by liquid chromatography–mass spectrometry using Biocrates AbsoluteIDQ-p180 kit. Genotyping of FTO rs9939609 was performed by real-time PCR (TaqMan™ MGB probes). Results Using OPLS-DA variable importance in projection (VIP), tryptophan was found to be among the metabolites with the 10 highest VIP scores. Pearson’s correlation analysis showed that kynurenine and tryptophan were positively correlated only in subjects with the rs9939609 A allele (n = 32, r = 0.56, p

N6-methyladenosine (m6A) regulates fat development in many ways. Low intramuscular fat (IMF) in rabbit meat seriously affects consumption. In order to improve meat quality, we explored the law of IMF deposition. FTO could increase the expression of APMAP and adipocyte differentiation through methylation. However, interference YTHDF2 can partially recover the influence of interference FTO on the APMAP gene and adipocyte differentiation. APMAP promoted the differentiation of adipocytes. Analysis of IMF and APMAP expression showed IMF content is positive with the expression level of the APMAP gene (p < 0.01). Conclusion: Together, FTO can regulate intramuscular fat by targeting the APMAP gene via an m6A-YTHDF2-dependent manner in Rex rabbits. The result provides a theoretical basis for the molecular breeding of rabbits.

(1) Background: obesity is a global public health problem; various factors have been associated with this disease, and genetic factors play a very important role. Previous studies in multiple populations have associated a gene with fat mass and obesity (FTO). Thus, the present work aims to identify and determine associations between genetic variants of FTO with indicators of overweight and obesity in the Mexican population. (2) Methods: a total of 638 subjects were evaluated to compile data on body mass index (BMI), the percentage of body fat (%BF), the waist circumference (WC), the serum levels of triglycerides (TG), and food consumption. A total of 175 genetic variants in the FTO gene were sampled by a microarray in the evaluated population, followed by association statistical analyses and comparisons of means. (3) Results: a total of 34 genetic variants were associated with any of the 6 indicators of overweight and obesity, but only 15 showed mean differences using the recessive model after the Bonferroni correction. The present study shows a wide evaluation of FTO genetic variants associated with a classic indicator of overweight and obesity, which highlights the importance of genetic analyses in the study of obesity.

Copyright of Saudi Medical Journal is the property of Saudi Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disorder caused by a complex interaction of genetic and environmental variables. T2DM is associated with transcription factor 7-like 2 (TCF7L2) and fat mass and obesityassociated (FTO) genetic polymorphism. Objectives: The goal of this study was to examine the common genetic risk factors of T2DM and related metabolic traits in Upper Egyptian population, in attempt to understand the genetic structure of T2DM in the Egyptian community. Methods and Materials: This case control study included 250 participants, 124 T2DM patients and 126 non-diabetics. Using mutagenically separated polymerase chain reaction (MS-PCR), genotyping of single nucleotide polymorphisms (SNP) rs7903146 of TCF7L2 and rs17817449 of FTO genes was carried out. Results: T allele of TCF7L2 variant rs7903146 confers a risk for T2DM (allelic OR=1.97, 95% CI: (1.34 to 2.88) p =<0.001). The minor G allele of FTO rs17817449 polymorphism was significantly higher in diabetics than controls (allelic OR=1.87, 95% CI=1.30 to 2.68, p<0.001). Genotype risk was evident under both recessive and dominant modes of inheritance (OR=3.18, CI (1.35-7.45), P =0.008, OR= 2.04, CI (1.23-3.38), p=0.006) for TCF7L2 and (OR= 2.55, CI (1.28 -5.09), p=0.008 and OR= 2.14, CI (1.25-3.63), p= 0.005) for FTO respectively Conclusion: TCF7L2 rs7903146 and FTO rs17817449 variant conferred risk for T2DM in Upper Egyptian population. The study noted the interaction between certain biological and environmental risk factors including BMI, age, and sex and the conferred genetic risk. [ABSTRACT FROM AUTHOR]

Fat mass and obesity-associated (FTO) gene is an obesity susceptibility gene and its relationship with the nonalcoholic fatty liver disease (NAFLD) remains unclear. This study aims to investigate the relationships of FTO gene variations with NAFLD risk in a Chinese male population.

Background: FTO gene is considered to play an important role in many metabolic diseases. Evidence from studies indicated the possible association between the FTO rs9939609 polymorphisms with serum lipid profile. Therefore, this study aimed to investigate the association of FTO rs9939609 polymorphism with lipid profile in Iranian women. Methods: This cross-sectional study was carried out on 380 adult women. Information about age, height, weight, BMI, physical activity, and dietary intake were collected. The serum levels of Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Triglyceride (TG), and total cholesterol were measured. The FTO gene was genotyped for rs9939609 polymorphism. The participants were divided into two groups of TT and AT/AA considering dominant model of FTO rs9939609 polymorphism. Results: General characteristics of the participants with different FTO genotypes were not significantly different. The lower levels of HDL were observed in AT/AA genotypes compared to the TT wild type genotype of FTO rs9939609 polymorphism (P = 0.004). Adjustments of age, BMI, and physical activity did not change the results. Conclusions: However, the significant association between FTO genotype and the HDL level was disappeared after further adjustments for dietary intake. Further studies are warranted to identify the underlying mechanisms of the possible association between FTO gene and serum lipid profile. [ABSTRACT FROM AUTHOR]

Obesity and type-2 diabetes mellitus (T2DM) have become a common and increasingly growing chronic non-communicable disease worldwide with potentially devastating complications and the FTO gene (rs9939609) are found to be associated with obesity and T2DM in several studies. So, the present review is aimed to investigate the current understanding of the effect of the FTO gene (rs9939609) on obesity and T2DM. PubMed, Medline, Google Scholar, Cochrane library, and several other databases were searched up from 2000 to 2019 to identify and select relevant studies. Research conducted using humans are only considered as eligible. Among the 17 prospective cohort studies, two have found no significant association between the FTO gene and type-2 diabetes (T2D), four studies revealed an association of the FTO gene with obesity and T2D and 11 studies identified a positive association of the FTO gene with obesity. The current study confirmed the significant association of the FTO gene with the risk of obesity and T2DM. Further studies should be conducted to identify the causal variant and the underlying mechanisms of the identified association. [ABSTRACT FROM AUTHOR]

Lubna Ibrahim Al Asoom,1 Dina Tariq Al Afandi,2 Aseel Salah Al Abdulhadi,3 Nazish Rafique,1 Shahanas Chathoth,4 Ahmad A Al Sunni1 1Physiology Department, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Pediatrics Department, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 3Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 4Biochemistry Department, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaCorrespondence: Lubna Ibrahim Al Asoom Email lasoom@iau.edu.saBackground: Obesity is a major health threat worldwide. It predisposes individuals to diabetes, cardiovascular complications, and cancer. Genetic and environmental factors are responsible for the increasing incidence of obesity. In this study, we investigated the genetic factors associated with obesity in young Saudi women.Subjects and Methods: In this cross-sectional study, 131 young Saudi female students were recruited. Body mass index (BMI), waist–hip ratio, blood glucose, triglyceride, cholesterol, HDL, LDL, and vitamin D3 levels of the subjects were determined. Twelve SNPs of different genes that showed a correlation with obesity in different population were tested, namely GNPDA2 (rs10938397), TCF7L2 (rs10885409), FTO (rs1477196), ADIPOQ (rs1501299), MC4R (rs17782313), ABCA1 (rs1800977), FTO (rs1861868), VDR (rs2228570), VDR (rs731236), VDR (rs7975232), ADIPOQ (rs266729), and PFPK (rs6602024). Student’s t-test was conducted for all parameters. Pearson correlation was performed to identify the correlated variables. The frequencies of different risk alleles were determined by direct counting of the test allele divided by the total number of alleles and compared.Results: Only two SNPs, rs1861868 of FTO and rs7975232 of VDR, of the twelve tested SNPs showed significant protective associations with the BMI with odds ratio 0.3886 (0.1761– 0.8572); p 0.0192 and odds ratio 0.4563 (0.2343– 0.8888); p 0.0211, respectively.Conclusion: The current study showed that minor alleles, “T” of FTO and “A” of VDR, might be protective factors against increased BMI in young Saudi female subjects. To elucidate this association, further studies with larger sample size involving both sexes are required.Keywords: BMI, obesity, body weight, FTO gene, VDR gene, polymorphism

FTO gene polymorphisms are associated with obesity and food intake. This study aimed to investigate the association of FTO rs9939609 polymorphism genotypes with serum glucose, lipid profile and serum hormones level. This cross-sectional study was carried out on 196 randomly selected overweight adults. Anthropometric measurements including weight, height, body mass index (BMI), fat mass, and fat-free mass were assessed. Serum TGs, total cholesterol, HDL cholesterol, LDL cholesterol, glucose and insulin levels were measured. The FTO gene was Genotyped for rs9939609 polymorphism. Dietary intake was assessed by avalid 168-item semi-quantitative food frequency questionnaire (FFQ). The homozygotes for the FTO rs9939609 risk allele (A) had higher serum leptin (p = 0.005, F: 5.131) and lower HDL (p = 0.001, F: 7.687) level than TT genotype. The differences between TT and AT genotypes were not significant. The association remained significant for HDL level after adjustments for age and sex, calorie intake, physical activity, and BMI. The association between rs9939609 polymorphism genotypes and leptin was disappeared after adjustments for calorie intake and physical activity. In conclusion, rs9939609 risk allele was associated with higher serum leptin and lower HDL levels in overweight people. Further studies are warranted.

Background: The roles of FTO gene and the level of serum 25-OH-vitamin D in obesity are frequently reported. This study aimed to investigate the interactions of serum 25-OH-vitamin D level, FTO and IRX3 genes expression, and FTO genotype in obese and overweight boys.Methods: This study was carried out on the 120 male adolescents with overweight in Tehran, Iran. Blood samples were collected from the participants in order to evaluate the serum level of 25-OH-vitamin D, the expression level of FTO and IRX3 genes, and FTO genotype for rs9930506 at baseline and after 18 weeks of the study.Results: In general, no significant association was found between serum 25-OH-vitamin D level and IRX3 and FTO genes expression. The results of linear regression on the relationship between 25-OH-vitamin D serum level and FTO and IRX3 genes expression based on FTO genotypes for rs9930506 indicated that in AA/AG genotype carriers, serum 25-OH-vitamin D level was positively associated with FTO gene expression (B = 0.07, p = 0.02) and inversely associated with IRX3 gene expression (B = - 0.07, p = 0.03). In GG carriers, serum 25-OH-vitamin D level was not associated with expression of IRX3 and FTO genes.Conclusion: There are significant interactions between 25-OH-vitamin D and the expression of FTO and IRX3 genes in the subset of obese patients with specific genotypes for FTO rs9930506. There was no association between serum 25-OH-vitamin D levels and the expression of FTO and IRX genes in individuals with a homozygous genotype for the risk allele of the FTO gene polymorphism. [ABSTRACT FROM AUTHOR]

Diabetes Mellitus (DM) is one of the important public health issues worldwide. The Fat mass obesity (FTO) gene rs-9939609 variant identified single nucleotide polymorphism (SNP) with the T to A missense mutation, and has a strong association with T2DM. FTO gene is present on chromosome "16q12.2" comprising of nine exons. FTO gene rs-9939609 a variant is commonly found in the Pakistani Population. The purpose of the study was to alert the population about the rs-9939609 variant SNP, having a strong association with T2DM. Total of 190 participants were included in the present cross-sectional study. To collect the samples non-probability convenience technique was used. subjects were recruited and divided into three groups, normal healthy subjects, obese and T2DM. The patients were selected from the Medicine department Jamshoro/Hyderabad by filling the pre-designed proforma, as well as verbal and written consent taken from study participants. To analysed the data ANOVA Post hoc (Tukey-test) was applied for comparison among groups (P < 0.05) and "SNP-STAT" online software was used for frequencies. The BMI, neck circumference, waist circumference and lipid profile, fasting blood sugar and HbA1c was found significant (p < 0.001) in both genders as compared to control. Homozygous and heterozygous distribution of allelic and genotyping frequency was found in study participants. 37.9 %T/A, 57.4% T/T, and A/A were 4.7%. The FTO gene rs-9939609 variant amplified and have an increased risk of developing T2DM in the Sindh population. Codominant model odd ratio of T/A showed 2.42 (CI) 1.23–3.84, with significant p < 0.032. The present study concluded that the FTO gene SNP rs-9939609 variant was found in the population of Hyderabad, Sindh and having strong association with T2DM and obese individuals. Increase BMI, neck and waist circumference are the biomarkers of obesity and causative factors of T2DM. [ABSTRACT FROM AUTHOR]