Fat Mass And Obesity-associated Gene Research Articles

Interaction Effects of FTO and MC4R Polymorphisms on Total Body Weight Loss, Post-Surgery Weight, and Post-Body Mass Index after Bariatric Surgery.

Bariatric surgery (BS) is considered the most effective intervention for patients with severe obesity and is used to maintain long-term weight loss and glycemic control. The aim of this study was to analyze the effects of genotypes and haplotypes of the fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes on total body weight loss (TBWL), post-surgery weight, and post-BMI after bariatric surgery. We retrospectively selected 101 patients from Bajio High Specialty Regional Hospital, León Guanajuato, México, who underwent Roux-en-Y gastric bypass (RYGB) to determine their body mass index (BMI), blood pressure, biochemical characteristics, and comorbidities. Post-surgery, patients were referred for registered anthropometry and blood pressure. Glucose, lipid and hepatic profiles, and insulin, leptin, and ghrelin levels were measured, and rs9939609, rs9930506, and rs1421085 FTO and rs17782313 MC4R polymorphisms were genotyped. Six (4-8) years after BS, post-surgery weight was greater in carriers of the rs9939609 and rs1421085 risk genotypes. TBWL was lower for the rs9930506 and rs1421085 risk genotypes. Insulin and HOMA-IR were greater in patients with the three FTO polymorphisms. There were significant interaction effects of the rs9930506 and rs1421085 FTO risk genotypes on weight and BMI in response to BS. No association was found with the MC4R polymorphism. The genotypes and haplotypes of the FTO gene influence post-surgery weight, TBWL, insulin levels, and HOMA-IR.

Study the Association of Fat Mass and Obesity-associated (FTO) Gene Polymorphisms (SNP rs9939609) with Biochemical Markers in Obese Iraqi Patients

This study aimed to evaluate the association of single nucleotide polymorphisms (SNP rs-9939609) of the fat mass and obesity-associated (FTO) gene with body mass index (BMI) and some biochemical markers in obese patients. The fat and mass obesity (FTO) gene variant specific single nucleotide polymorphism (SNP rs-9939609) with the T to A missense mutation may have a powerful association with obesity. This case-control study included 106 obese patients (57 males and 49 females) and 80 healthy control (40 males and 40 females). DNA was extracted from whole blood, and then the tetra-primer amplification refractory mutation system - polymerase chain reactions (ARMS.PCR) technique was used to limit the single nucleotide gene polymorphisms (rs9939609) of the FTO gene. Lipid profile, glycated hemoglobin (HbA1C), fasting blood sugar, insulin and FTO concentrations were measured by standard methods. In this study, the A allele in the rs9939609 was at a higher frequency of 35 (33.1%) in the obese patients and at a significant p-value = 0.039 compared with control 15 (18.7%). It significantly increased in the additive model and allele frequency (p= 0.003, 0.002 respectively). The rs9939608 SNP showed a significant association with increased BMI, insulin and homeostatic model assessment-insulin resistance (HOMO-IR) with p-values of 0.001, 0.001 and 0.028 respectively. After making adjustments for age and sex, lower levels of high-density lipoprotein (HDL) were observed in the AA and TA genotypes compared to the TT genotype (p = 0.004). While, no significant differences were recorded between the rs9939608 SNP and HbA1C, total cholesterol (TC), triglyceride (TG), very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) in obese patients

<i>Artocarpus Communis</i> Seed Regulates P53, IRS, HsD17β2, FTO, and CYP11a Genes in Polycystic Ovarian Syndrome Rats

Polycystic ovarian syndrome (PCOS) is a prevalent endocrine illness that affects 5-10% of reproductive women globally. It is a multifaceted hormonal disorder characterized by the involvement of numerous molecular mechanisms that contribute to its development. This study investigates the effect of <em>Artocarpus communis </em>seed on the hormonal imbalance and P53, IRS, HsD17β2, FTO, and CYP11a genes expression in the ovaries of letrozole-induced polycystic ovarian syndrome rats. To induce PCOS in 30 female Wistar rats, letrozole was administered at a dosage of 1 mg/kg. For 12 days, <em>Artocarpus communis </em>seed aqueous extract (100 and 250 mg/kg body weight) and Clomiphene citrate (1 mg/kg body weight), a standard medication, were given. ELISA assessed luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels. The levels of P53, IRS, HsD17β2, FTO, and CYP11a gene expression in the ovaries were assessed. The aqueous extract reduced LH and increased FSH levels in Letrozole-induced PCOS rats. Additionally, seed aqueous extract (250 mg/kg bw) regulated the expression of P53, type 2 17-HSD (17-HSD), fat mass and obesity-associated (FTO), 11a-hydroxylase/17,20-desmolase (CYP11a), and insulin receptor substrate (IRS) genes in the ovaries of PCOS rats. Therefore, <em>Artocarpus communis</em> seed might have multifaceted effects on molecular pathways associated with PCOS, potentially normalizing androgen metabolism, hormonal imbalance, and ovarian function.

Study of Genetic Drifts in Some Fat Mass and Obesity Associated Gene Variatiants in Type 2 Diabetics in Some Ethinic Groups Residing in Delta State, Nigeria

Aim: Detailing and distribution of some predominant FTO genes among subjects with diabetes mellitus selected from Igbo, Ika, Ijaw and Isoko tribes of Delta state, Nigeria.
 Study Design: Case-control, observational study.
 Place and Duration of Study: Federal Medical Center, Asaba, Delta State and Safety Molecular Pathology Laboratory Enugu, Nigeria, between March 2020 and Febuary 2022.
 Methodology:100 subjects (20 diabetic and 5 non diabetic from each of the four tribes; age range; 28-74 years) Venous blood was collected for the assay of FBS, Hb1ac and molecular assay of four variants of FTO (Fat Mass and Obesity Associated) gene. Results obtained were statistically analysed.
 Result: The genotypes identified in the subjects were AA, GA, GG, AC, CC, TT, and AT. AA (Ijaw 17, Urhobo 18, Ika 18, Igbo 19) and GG (Ijaw 17, Urhobo 18, Ika 19, Igbo 18) had highest level of occurrence in all tribes. Recombinant genotype and recessive allele had higher number of subjects as compared to the originating genotypes. Hardy- Weinberg statistics demonstrated significant genetic deviations in rs2388405(AA -0.12 x2 =0.0002, GA 0.12 x2=0.002) rs201041270(GG-0.12 x2 =0.0002, GA 2.12 x2=0.002), and rs8050136 (CC -0.34 x2 =0.001, AC 2.32, x2=0.05) proving a chance of finding new SNP in the studied population with a probability of 2.25 as seen in the odd ratio of T allele in Igbo tribe.
 Conclusion: Statistically significant genetic drifts exist in the studied population.

Fat mass and obesity-associated (FTO) gene is essential for insulin secretion and β-cell function: In vitro studies using INS-1 cells and human pancreatic islets

AimsIn this study, we investigated the role of the FTO gene in pancreatic β-cell biology and its association with type 2 diabetes (T2D). To address this issue, human pancreatic islets and rat INS-1 (832/13) cells were used to perform gene silencing, overexpression, and functional analysis of FTO expression; levels of FTO were also measured in serum samples obtained from diabetic and obese individuals. ResultsThe findings revealed that FTO expression was reduced in islets from hyperglycemic/diabetic donors compared to normal donors. This reduction correlated with decreased INS and GLUT1 expression and increased PDX1, GCK, and SNAP25 expression. Silencing of Fto in INS-1 cells impaired insulin release and mitochondrial ATP production and increased apoptosis in pro-apoptotic cytokine-treated cells. However, glucose uptake and reactive oxygen species production rates remained unaffected. Downregulation of key β-cell genes was observed following Fto-silencing, while Glut2 and Gck were unaffected. RNA-seq analysis identified several dysregulated genes involved in metal ion binding, calcium ion binding, and protein serine/threonine kinase activity. Furthermore, our findings showed that Pdx1 or Mafa-silencing did not influence FTO protein expression. Overexpression of FTO in human islets promoted insulin secretion and upregulated INS, PDX1, MAFA, and GLUT1 expression. Serum FTO levels did not significantly differ between individuals with diabetes or obesity and their healthy counterparts. ConclusionThese findings suggest that FTO plays a crucial role in β-cell survival, metabolism, and function and point to a potential therapeutic utility of FTO in T2D patients.

LncRNA FTO-IT1 promotes glycolysis and progression of hepatocellular carcinoma through modulating FTO-mediated N6-methyladenosine modification on GLUT1 and PKM2

BackgroundLong non-coding RNAs (LncRNAs) have been extensively studied to play essential roles in tumor progression. However, more in-depth studies are waiting to be solved on how lncRNAs regulate the progression of hepatocellular carcinoma (HCC).MethodsDifferent expression levels of lncRNAs in HCC cells were compared by analysis of Gene Expression Omnibus and The Cancer Genome Atlas databases. The effects of lncRNA FTO Intronic Transcript 1 (FTO-IT1) on HCC cells were assessed by gain- and loss-of-function experiments. Colony formation assay, Edu assay, glucose uptake and lactic acid production assay were performed to evaluate the regulation of proliferation and glycolysis of HCC cells by FTO-IT1. The binding between protein interleukin enhancer binding factor 2/3 (ILF2/ILF3) and FTO-IT1 was determined by RNA pull-down, mass spectroscopy and RNA immunoprecipitation experiments. RNA stability assay, quantitative reverse transcription PCR and Western blot were employed to determine the regulatory mechanisms of FTO-IT1 on fat mass and obesity-associated (FTO). Methylated RNA immunoprecipitation assay was used to assessed the regulation of key enzymes of glycolysis by FTO. The role of FTO-IT1/FTO in vivo was confirmed via xenograft tumor model.ResultsLncRNA FTO-IT1, an intronic region transcript of FTO gene, was highly expressed in HCC and associated with poor prognosis of patients with HCC. FTO-IT1 was related to proliferation and glycolysis of HCC cells, and contributed to the malignant progression of HCC by promoting glycolysis. Mechanistically, FTO-IT1 induced stabilization of FTO mRNA by recruiting ILF2/ILF3 protein complex to 3’UTR of FTO mRNA. As a demethylase for N6-methyladenosine (m6A), FTO decreased m6A modification on mRNAs of glycolysis associated genes including GLUT1, PKM2, and c-Myc which alleviated the YTH N6-methyladenosine RNA binding protein 2 (YTHDF2)-mediated mRNA degradation. Therefore, the upregulated expression of FTO-IT1 leaded to overexpression of GLUT1, PKM2, and c-Myc by which enhanced glycolysis of HCC. Meanwhile, it was found that c-Myc transcriptional regulated expression of FTO-IT1 by binding to its promoter area under hypo-glucose condition, forming a reciprocal loop between c-Myc and FTO-IT1.ConclusionsThis study identified an important role of the FTO-IT1/FTO axis mediated m6A modification of glycolytic genes contributed to glycolysis and tumorigenesis of HCC, and FTO-IT1 might be served as a new therapeutic target for HCC.

Role of rs9939506 polymorphism of FTO gene in resistance to eating in male adolescents

BackgroundSingle 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.MethodsThe 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.ResultsAccording 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.ConclusionAccording 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.

Effects of dietary supplementation with algae, sunflower oil, or soybean oil, and age on fat content, fatty acid profile and the expression of related genes in rabbits

>Abstract The aim of this study was determine the effect of different dietary supplements (algae, sunflower oil, or soybean oil) and age (12 and 18 weeks) on the fat content, fatty acid (FA) profile, and expression of the fat mass and obesity associated (FTO) and fatty acid binding protein 4 (FABP4) genes in rabbit muscle. Rabbits (n = 160) were randomly divided into four groups. The control group (C) received non-supplemented pellets, while in the other groups the pellet contained 1% algae (A), 3% sunflower oil (OS), or 3% soybean (SO) oil. Soybean and sunflower oil (3%) in the diet increased the linoleic acid (LA) content in meat of 12-week-old rabbits. The use of algae (1%) in the diet increased the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared with the vegetable oil and control groups, and decreased the n-6/n-3 ratio. The effect of the diet on FTO and FABP4 gene expression depended on the age of the rabbits. In older animals (18 weeks of age) the expression of these genes was highest in the group with 1% algae. Furthermore, the FA profile and FTO and FABP4 gene expression were affected by the age of rabbits, but not by sex. The results showed that diet is an important tool to modulate the FA profile in rabbit meat by changing the expression of fat metabolism–related genes.

RS17817449 FTO gene variation associated with familial disease burden rather than individual risk for breast cancer

Introduction: Breast cancer (BC) is the most common malignancy in the female population globally. Obesity is associated with an increased risk of postmenopausal BC, BC recurrence, and mortality. Fat mass and obesity-associated (FTO) gene polymorphisms have attracted the most attention due to several single-nucleotide polymorphisms (SNPs) that may have an impact on obesity and different types of cancer. The primary goal of our work was to assess the association of the SNP rs17817449 FTO, physical status/metabolic changes, and dietary habits with the occurrence of BC. Methods: We conducted research as a population-genetic study including 93 women with a diagnosis of BC during their lifetime. Genomic DNA was extracted from the swabs of the buccal mucosa. Genotyping was achieved by polymerase chain reaction-restriction fragment length polymorphism. The IBM SPSS Statistics program v. 23.0 was used for statistical analysis. All values of p < 0.05 were considered statistically significant. Results: The risk genotype of the FTO gene (rs17817449) GG was detected in 16 subjects (17.2%), the heterozygous TG in 46 subjects (49.5%), while the normal genotype TT was recorded in 29 subjects (31.2%). We found no statistically significant difference in the body mass index values of the three genotype groups, p = 0.72, χ2 = 2.1 and no significant relationship between the allelic or genotypic frequencies of the rs17817449 FTO gene polymorphism and other variables examined in our study. Analysis of the distribution of hereditary diseases in the family according to the molecular subtype of BC showed statistically significant p-values, p = 0.02. Conclusion: While previous research has suggested a potential link between FTO gene polymorphism, obesity, and BC, our study did not find a statistically significant association between the aforementioned variables. Future studies with a larger number of subjects in different populations should confirm the role of the FTO genotype in the risk of BC.

The effect of FTO gene rs9939609 polymorphism on the association between colorectal cancer and different types of dietary fat intake: a case-control study

BackgroundColorectal cancer (CRC) is one of the most common cancers in the world. Some dietary factors such as fat intake have been identified as the risk factors for CRC. This study aimed to investigate the effect of fat mass and obesity-associated (FTO) gene rs9939609 polymorphism on the association between CRC and different types of dietary fats.MethodsThis case-control study was performed on 135 CRC cases and 294 healthy controls in Tehran, Iran. Data on demographic factors, anthropometric measurements, physical activity, the intake of different types of dietary fats, and FTO gene rs9939609 polymorphism was collected from all participants. The association between cancer and dietary fat intake in individuals with different FTO genotypes was assessed using different models of logistic regression.ResultsOleic acid intake was higher in the case group compared to the control group in both people with TT (7.2±3.46 vs. 5.83±3.06 g/d, P=0.02) and AA/AT genotypes (8.7±6.23 vs. 5.57 ±3.2 g/d, P<0.001). Among carriers of AA/AT genotypes of FTO rs9939609 polymorphism, a positive association was found between CRC and higher intakes of oleic acid (OR=1.12, CI95% 1.03–1.21, P=0.01) and cholesterol (OR=1.01, CI95% 1.00–1.02; P=0.01) after adjusting for age, sex, physical activity, alcohol use, smoking, calorie intake, and body mass index.ConclusionHigher intakes of cholesterol and oleic acid were associated with a higher risk of CRC in FTO-risk allele carriers. The association of CRC and dietary fat may be influenced by the FTO genotype. Further longitudinal studies are warranted to confirm these findings.

Emerging Role and Mechanism of the FTO Gene in Cardiovascular Diseases.

The fat mass and obesity-associated (FTO) gene was the first obesity-susceptibility gene identified through a genome-wide association study (GWAS). A growing number of studies have suggested that genetic variants of FTO are strongly associated with the risk of cardiovascular diseases, including hypertension and acute coronary syndrome. In addition, FTO was also the first N6-methyladenosine (m6A) demethylase, suggesting the reversible nature of m6A modification. m6A is dynamically deposited, removed, and recognized by m6A methylases, demethylases, and m6A binding proteins, respectively. By catalyzing m6A demethylation on mRNA, FTO may participate in various biological processes by modulating RNA function. Recent studies demonstrated that FTO plays a pivotal role in the initiation and progression of cardiovascular diseases such as myocardial fibrosis, heart failure, and atherosclerosis and may hold promise as a potential therapeutic target for treating or preventing a variety of cardiovascular diseases. Here, we review the association between FTO genetic variants and cardiovascular disease risk, summarize the role of FTO as an m6A demethylase in cardiovascular disorders, and discuss future research directions and possible clinical implications.

The obesity associated FTO gene polymorphism and the risk of preeclampsia in Iranian women: A case–control study

ABSTRACT Background Preeclampsia (PE) is one of the leading disorders in pregnant women with maternal and fetal complications. Obesity is considered an important risk factor for the development of PE. Genetic variations in fat mass and obesity associated (FTO) gene may play a role in the development of PE. This study aimed to investigate the possible association between FTO gene rs9939609 and PE risk in a sample of Iranian pregnant women. Material and methods In this case–control study, 312 pregnant women were included, including 128 with PE and 184 without PE. Demographic data and blood samples were obtained from all individuals. The genotyping of rs9939609 polymorphisms was performed by the tetra‐primer amplification refractory mutation system‐polymerase chain reaction (TP‐ARMS‐PCR) method, and the results of TP‐ARMS‐PCR were confirmed using DNA sequencing. Results The genotype frequency was 50%, 47.7%, and 2.3% in pregnant patients and 37%, 47.8%, and 15.2% in healthy controls for TT, AT, and AA, respectively. The risk of PE was significantly reduced in the pregnant women having the AA genotype. Conclusion Based on the results of the present study, rs9939609 polymorphism in the FTO gene may play a protective role against PE. However, further studies are warranted.

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.

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.

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.&#x0D; Study Design: Case-controlled observational study.&#x0D; Place and Duration of Study: Federal Medical Centre, Asaba, Delta State and Safety Molecular Pathology Laboratory, Enugu, Nigeria, between March 2020 and February 2022.&#x0D; 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 &amp; 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.&#x0D; 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&gt;T), rs116753298 (T&gt;C), rs201041270 (A&gt;G), rs531215275 (A&gt;C), rs146056278 (C&gt;T), rs1410999299 (G&gt;A), rs79206939 (A&gt;G), rs145884431(G&gt;A), rs61743972 (G&gt;A), rs201496428 (C&gt;T), rs146138389 (T&gt;C), rs886052102 (A&gt;G), rs144743617 (G&gt;A), rs886052103 (T&gt;A), rs9939609 (A&gt;T) and rs8050136 (A&gt;C). However, no significant differences in analyzed genotype frequencies were found between T2D and healthy controls.&#x0D; 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.

Gene polymorphisms associated with heterogeneity and senescence characteristics of sarcopenia in chronic obstructive pulmonary disease.

Sarcopenia, or loss of skeletal muscle mass and decreased contractile strength, contributes to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). The severity of sarcopenia in COPD is variable, and there are limited data to explain phenotype heterogeneity. Others have shown that COPD patients with sarcopenia have several hallmarks of cellular senescence, a potential mechanism of primary (age-related) sarcopenia. We tested if genetic contributors explain the variability in sarcopenic phenotype and accelerated senescence in COPD. To identify gene variants [single nucleotide polymorphisms (SNPs)] associated with sarcopenia in COPD, we performed a genome-wide association study (GWAS) of fat free mass index (FFMI) in 32 426 non-Hispanic White (NHW) UK Biobank participants with COPD. Several SNPs within the fat mass and obesity-associated (FTO) gene were associated with sarcopenia that were validated in an independent COPDGene cohort (n=3656). Leucocyte telomere length quantified in the UK Biobank cohort was used as a marker of senescence. Experimental validation was done by genetic depletion of FTO in murine skeletal myotubes exposed to prolonged intermittent hypoxia or chronic hypoxia because hypoxia contributes to sarcopenia in COPD. Molecular biomarkers for senescence were also quantified with FTO depletion in murine myotubes. Multiple SNPs located in the FTO gene were associated with sarcopenia in addition to novel SNPs both within and in proximity to the gene AC090771.2, which transcribes long non-coding RNA (lncRNA). To replicate our findings, we performed a GWAS of FFMI in NHW subjects from COPDGene. The SNP most significantly associated with FFMI was on chromosome (chr) 16, rs1558902A>T in the FTO gene (β=0.151, SE=0.021, P=1.40×10-12 for UK Biobank |β=0.220, SE=0.041, P=9.99×10-8 for COPDGene) and chr 18 SNP rs11664369C>T nearest to the AC090771.2 gene (β=0.129, SE=0.024, P=4.64×10-8 for UK Biobank |β=0.203, SE=0.045, P=6.38×10-6 for COPDGene). Lower handgrip strength, a measure of muscle strength, but not FFMI was associated with reduced telomere length in the UK Biobank. Experimentally, in vitro knockdown of FTO lowered myotube diameter and induced a senescence-associated molecular phenotype, which was worsened by prolonged intermittent hypoxia and chronic hypoxia. Genetic polymorphisms of FTO and AC090771.2 were associated with sarcopenia in COPD in independent cohorts. Knockdown of FTO in murine myotubes caused a molecular phenotype consistent with senescence that was exacerbated by hypoxia, a common condition in COPD. Genetic variation may interact with hypoxia and contribute to variable severity of sarcopenia and skeletal muscle molecular senescence phenotype in COPD.

Assessment of health risks caused by overweight in children depending on the FTO gene rs9939609 polymorphism

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.

Оценка риска избыточной массы тела у детей в зависимости от полиморфизма rs9939609 генa FTO

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.

Effects of Helicobacterpylori on the expression of the FTO gene and its biological role in gastric cancer.

Helicobacter pylori (Hp) is a primary risk factor for gastric cancer. The fat mass and obesity-associated (FTO) gene is associated with the development and progression of various cancer types such as glioma, leukemia, breast cancer and colorectal cancer. The aim of the present study was to investigate the effect of Hp infection on the expression of FTO and its roles in gastric cancer. It was found that the expression levels of both FTO mRNA and protein were significantly increased in Hp-infected human gastric mucosal epithelial cells and Mongolian gerbil gastric tissues. The expression of FTO in gastric cancer tissues was higher than that in para-cancer tissues. Data from The Cancer Genome Atlas demonstrated that FTO expression in gastric cancer tissues was significantly higher than that in normal tissues. Patient survival rate was significantly decreased in patients with high expression levels of FTO. It was also demonstrated that FTO expression was associated with several pathological parameters, such as tumor stage, metastasis stage and the American Joint Committee on Cancer stage. The FTO gene was positively correlated with 16,601 genes in gastric cancer and negatively correlated with 3,623 genes. Gene Ontology enrichment analysis demonstrated that FTO was significantly enriched in the regulation of gene expression and oxidative RNA demethylase activity, and it was associated with components such as the RNA N6-methyladenosine methyltransferase complex and nuclear speckle. In addition, knockdown of the FTO gene inhibited the migration and invasion of Hp-infected cells. In conclusion, the data suggests that Hp infection leads to upregulation of the FTO gene, which may be related to patient survival rate, tumor staging and other pathological parameters of patients with gastric cancer. It also suggests that FTO promotes proliferation and migration of gastric cancer cells, which may be involved in the pathogenesis of Hp-induced gastric cancer.

Screening of Exons 4-9 Polymorphisms of FTO Gene in Endometrial and Ovarian Cancers.

Endometrial and ovarian tumours are almost mechanistically affected by reproductive hormones. Ovarian cancer may be explained as metastatic or synchronous primary ovarian cancer, and the specific diagnosis is a challenge. This study aimed to investigate the mutations in fat mass and obesity-associated (FTO) genes and investigated the association of these mutations with the risk of endometrial and ovarian cancers as well as with cancer grade and stage. Blood samples were collected from 48 endometrial and ovarian cancer cases and 48 healthy women. Genomic DNA was extracted, and PCR was done to amplify FTO exons 4-9. Sanger sequencing identified 6 different novel mutations submitted to DDBJ: p.W278G and p.G284G in exon 4, p.S318I and p.A324G in exon 5 and two mutations in intron 4. Other mutations were also detected in FTO gene sequencing results, rs112997407 in intron 3, rs62033438, rs62033439, rs8048254 and rs8046502 in intron 4. The novel p.W278G, p.S318I and p.A324G mutations were predicted to be damaging. We did not find a significant association for all variables with cancer risk or clinical stage and grade except for rs62033438 variants, which showed a significant association with cancer grade, especially AA genotype (OR= 15, 95% CI:1.32 -169.88, P= 0.03). In conclusion, the statistical analysis did not clarify whether FTO mutations are implicated in cancer. Further studies with more samples are recommended to provide a more accurate picture of the correlation between FTO mutations and endometrial and ovarian cancer susceptibility.