Fat Mass And Obesity-associated Gene Polymorphisms Research Articles

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 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.

The Effect of Association between Fat Mass and Obesity-associated Gene Polymorphism (rs9939609) on the Body Composition of Older People: A Systematic Review.

The aging population is growing faster than any other age group worldwide. Associated with aging, the prevalence of overweight and obesity is a potential risk factor for the development and aggravation of numerous pathologies. A genetic factor often associated with obesity is the fat mass and obesity-associated (FTO) (rs9939609) gene polymorphism, which has been extensively investigated in children, young, and adults. However, few studies have been carried out on the older population. This review aimed to verify the influence of the FTO (rs9939609) gene polymorphism on the body composition of the older population. We conducted a systematic review and meta-analysis on PubMed, Scielo, and LILACS databases. Statistical analysis for meta-analysis was performed using mean values of Body Mass Index (BMI) and standard deviations. The results did not show significant differences between FTO genotypes and BMI values (-0.32, 95% CI -0.45 to -0.19, I2 = 0%, p = 0.52). However, 59% of the studies identified some influence on body composition, obesity, or comorbidities. Few publications verify FTO polymorphism effects on specific groups of the older population, suggesting a reduction in the influence of this gene on the BMI with advancing age. However, we believe that more controlled studies in older populations should be performed.

Association of fat mass and obesity-associated (FTO) gene polymorphisms with non-communicable diseases (NCDs) in the Iranian population: A systematic review of observational studies.

Single nucleotide polymorphisms have been implicated in various diseases, most notably non-communicable diseases (NCDs). The aim of this study was to review available evidence regarding associations between FTO polymorphisms and NCDs in the Iranian population. A comprehensive search was conducted through PubMed/Medline and Scopus databases up to December 2021, as well as reference lists of pertinent articles and key journals. All observational studies that examined the association between FTO gene polymorphisms and NCDs in the Iranian population were included. There was no limitation on the publication year. The Newcastle-Ottawa Scale (NOS) was used to assess the study's quality. The initial search yielded 95 studies, of which 30 studies were included in the current systematic review. The underlying disorders were obesity, type 2 diabetes, breast and colorectal cancers, depression, and metabolic syndrome. These studies found an association between FTO gene polymorphisms and obesity in the Iranian population, but the relationship with other NCDs was debatable. Even though, other diseases such as diabetes and metabolic syndrome, which are closely related to obesity, may also be associated with FTO gene polymorphisms. FTO gene polymorphism appears to play a role in the occurrence of NCDs. Some of the study results may be misleading due to ethnic differences and the effect of other genetic factors on disease onset, which needs to be investigated further. Finally, FTO gene polymorphisms can be studied as a preventive or therapeutic target. The online version contains supplementary material available at 10.1007/s40200-022-01139-4.

Gut microbiota modulates differential lipid metabolism outcomes associated with FTO gene polymorphisms in response to personalized nutrition intervention.

BackgroundInterindividual differences in response to personalized nutrition (PN) intervention were affected by multiple factors, including genetic backgrounds and gut microbiota. The fat mass and obesity associated (FTO) gene is an important factor related to hyperlipidemia and occurrence of cardiovascular diseases. However, few studies have explored the differences in response to intervention among subjects with different genotypes of FTO, and the associations between gut microbiota and individual responses.ObjectiveTo explore the differential lipid metabolism outcomes associated with FTO gene polymorphisms in response to PN intervention, the altered taxonomic features of gut microbiota caused by the intervention, and the associations between gut microbiota and lipid metabolism outcomes.MethodsA total of 400 overweight or obese adults were recruited in the study and randomly divided into the PN group and control group, of whom 318 completed the 12-week intervention. The single nucleotide polymorphism (SNP) of rs1121980 in FTO was genotyped. Gut microbiota and blood lipids were determined at baseline and week 12. Functional property of microbiota was predicted using Tax4Fun functional prediction analysis.ResultsSubjects with the risk genotype of FTO had significantly higher weight and waist circumference (WC) at baseline. Generalized linear regression models showed that the reduction in weight, body mass index (BMI), WC, body fat percentage, total cholesterol (TCHO), and low-density lipoprotein (LDL) was greater in subjects with the risk genotype of FTO and in the PN group. Significant interaction effects between genotype and intervention on weight, BMI, WC, TCHO, and LDL were found after stratifying for specific genotype of FTO. All subjects showed significant increasement in α diversity of gut microbiota after intervention except for those with the non-risk genotype in the control group. Gut microbiota, including Blautia and Firmicutes, might be involved in lipid metabolism in response to interventions. The predicted functions of the microbiota in subjects with different genotypes were related to lipid metabolism-related pathways, including fatty acid biosynthesis and degradation.ConclusionSubjects with the risk genotype of FTO had better response to nutrition intervention, and PN intervention showed better amelioration in anthropometric parameters and blood lipids than the control. Gut microbiota might be involved in modulating differential lipid metabolism responses to intervention in subjects with different genotypes.Trial registration[Chictr.org.cn], identifier [ChiCTR1900026226].

FTO genotype was associated with breast cancer in HER2 negative patients.

The fat mass and obesity-associated (FTO) gene may influence the risk of breast cancer (BC). The single nucleotide polymorphisms (SNPs) of FTO gene may exert different impacts on different types of BC. In this study, we investigated the association between FTO SNP rs9939609 and the status of estrogen receptor (ER), progesterone receptor (PR), P53, and human epidermal growth factor receptor-2 (HER-2) in BC patients. Our case-control study was included 540 Iranian participants aged 35 to 70 (180 women with BC as the case group and 360 healthy controls). After genotyping for risk allele rs9939609 of the FTO gene, a logistic regression was applied to elucidate the association between FTO SNP rs9939609 and BC risk based on the receptor status. The number of HER-2 negative patients was significantly higher in FTO rs9939609 risk allele carrier group (61.5% vs. 41.4%, P<0.05). A significant association was found between BC and rs9939609 FTO gene polymorphism only in HER2 negative BC patients (OR=1.79, CI95%: 1.2-3.56, P=0.03). No association was identified between FTO rs9939609 polymorphism and the status of ER, PR, and P53. We indicated that FTO SNP rs9939609 can be a potential therapeutic target particularly in HER-2 negative BC cases. The importance of this risk allele in BC pathogenesis needs to be further highlighted.

FTO Gene Polymorphisms at the Crossroads of Metabolic Pathways of Obesity and Epigenetic Influences.

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.

Serum spexin, adiponectin and leptin levels in polycystic ovarian syndrome in association with FTO gene polymorphism.

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinopathy among reproductive-aged women and related with body mass and insulin resistance. Adipocytokines produced by adipose tissue seems to take part in the hormonal and metabolic alterations that arise in PCOS. Fat mass and obesity associated (FTO) gene is linked with body mass index (BMI) and diabetes. Aims - To investigate the association between fat mass related adipocytokines and single nucleotide polymorphisms (SNPs) (rs9939609 T/A) in the FTO gene in women with PCOS. Study design - Cross-sectional study MATERIAL AND METHODS: FTO+rs9939609 gene polymorphism and serum spexin, adiponectin and leptin levels were determined in 91 PCOS women and 86 healthy controls. Study participants were subdivided according to BMI and comparisons were made within each group. Serum spexin levels were not differed between study groups. Serum levels of adiponectin were found to be decreased in PCOS women with BMI lower than 25 kg/m2 (10.1 ± 5.6 vs 14.1 ± 9.1, p = 0.015). Serum leptin levels were elevated in obese PCOS women compared to healthy control group (2197.9 ± 596.3 pg/mL vs 1535.9 ± 812.1 pg/mL, p = 0.001). The prevalence of A risk allele of SNP rs9939609 was more frequent in PCOS patients than in the control group. PCOS risk was found to increase 3 times more in AA genotype when compared with TT genotype (OR = 3.04 95% CI: 1.243-7.309; p = 0.013). Serum adiponectin and leptin levels may serve as independent markers for PCOS diagnosis. Moreover, the FTO+rs9939609 gene polymorphism increase susceptibility to PCOS development independent from serum adipocytokine levels.

Are the FTO Gene Polymorphisms Associated with Colorectal Cancer? A Meta-analysis.

Colorectal cancer (CRC) is reported to be associated with some gene polymorphisms. However, the effect of the fat mass and obesity associated (FTO) gene on colorectal cancer is not yet clear. This meta-analysis aimed to investigate the association of the FTO gene polymorphism and colorectal cancer. PubMed, Web of science, Scopus, and Embase were explored to identify the studies investigating the relationship between rs9939609 and rs17817449 polymorphisms of FTO gene and colorectal cancer, and the published papers from 2000 to 2019were collected. This meta-analysis was conducted by using a random-effects model for the best estimation of the desired outcomes. In this study, 1528 studies were initially included and five eligible case-control studies including 13,460 cases and 22,578 controls were eligible for further analyses. No significant association was found between risk allele of FTO rs9939609 (OR = 0.98, 0.87-1.1) and rs17817449 (OR = 0.9, 0.79-1.03) polymorphisms and colorectal cancer risk. The subgroup analyses considering the source of the control group and race found no significant association between FTO polymorphisms and the risk of colon cancer. This study indicated that rs9939609 and rs17817449 FTO gene polymorphisms are not associated with colorectal cancer risk. Individual studies involving different FTO polymorphisms are needed to further evaluation of the associations between the FTO gene and colon cancer.

Interactions of anthropometric indices, rs9939609 FTO gene polymorphism and breast cancer: A case-control study.

Contradictory results were reported on the effect of fat mass‐ and obesity‐associated (FTO) gene and anthropometric measurements on breast cancer (BC). This study aimed to assess the interactions between rs9939609 polymorphism of FTO gene, anthropometric indices and BC risk in Iranian women. This case‐control study was performed on 540 women including 180 women with BC and 360 healthy women in Tehran, Iran. Physical activity and dietary intakes were assessed by validated questionnaires. Data on sociodemographic and pathologic factors of the participants as well as their blood samples were collected. The rs9939609 FTO gene polymorphism was genotyped using the tetra‐primer amplification refractory mutation system‐polymerase chain reaction (T‐ARMS‐PCR). No significant association was found between BC and risk allele of FTO rs9939609 polymorphism after adjustments for the confounders. However, there was a significant association between rs9939609 polymorphism risk allele and BC risk in females with overweight, even after adjusting for age, family history of BC, abortion, BMI and the number of pregnancies (P < .05). The association was disappeared after further adjustments for lifestyle factors including smoking, alcohol consumption, calorie and macronutrients intake, and physical activity. The FTO gene polymorphism was associated with the risk of BC in overweight individuals. This association was influenced by environmental factors including diet, alcohol consumption and smoking. Future studies are required to confirm the association between the FTO gene and BC in overweight females and to identify the underlying mechanisms.

No Association Between FTO Gene Polymorphisms and Central Nervous System Tumor Susceptibility in Chinese Children.

BackgroundCentral nervous system (CNS) tumor is a malignancy commonly seen occurring in childhood, worldwide. Fat mass and obesity-associated (FTO) enzyme, initially identified as an obesity-related protein, also functions as a susceptibility gene for cancers. However, predisposing effect of FTO gene single nucleotide polymorphisms (SNPs) on CNS tumor risk remains unknown.MethodsHerein, we genotyped 314 CNS tumor patients and 380 healthy controls samples from three hospitals to explore whether FTO gene SNPs impact CNS tumor risk. TaqMan SNP genotyping assay was applied for the genotyping. Odds ratios (ORs) and 95% confidence intervals (CIs), generated from multinomial logistic regression, were applied to determine the associations of SNPs (rs1477196 G>A, rs9939609 T>A, rs7206790 C>G, and rs8047395 A>G) in FTO gene with risk of CNS tumor.ResultsWe failed to detect significant associations between FTO gene SNPs and CNS tumor risk, either in single-locus or combined analysis. A significantly increased ependymoma risk was found for carriers with 3–4 risk genotypes in comparison to 0–2 risk genotypes (adjusted OR=1.94, 95% CI=1.11–3.37, P=0.020).ConclusionOur data indicated that FTO gene SNPs are unlikely to have large effects on CNS tumor risk but may have weaker effects.

FTO - A Common Genetic Basis for Obesity and Cancer.

In recent years, the prevalence of obesity and cancer have been rising. Since this poses a serious threat to human health, the relationship between the two has attracted much attention. This study examined whether fat mass and obesity-associated (FTO) genes are linked, taking into account a Genome-wide Association Study (GWAS) that revealed multiple single nucleotide polymorphism sites (SNPs) of the FTO gene, indicating an association between obesity and cancer in different populations. FTO proteins have been proved to participate in adipogenesis and tumorigenesis with post-transcriptional regulation of downstream molecular expression or through the target of the mammalian target protein rapamycin (mTOR). FTO inhibitors have also been found to share anti-obesity and anti-cancer effects in vivo. In this review, we comprehensively discuss the correlation between obesity and cancer by measuring FTO gene polymorphism, as well as the molecular mechanism involved in these diseases, emphasizing FTO as the common genetic basis of obesity and cancer.

Association of fat mass and obesity associated gene polymorphism with the risk of gestational diabetes

Objective: The aim of this study is to investigate the relationship between fat mass and obesity associated (FTO) gene polymorphism and the risk of gestational diabetes mellitus (GDM), and provide clues and basis for the study of GDM mechanism. Methods: The case group of GDM pregnant women who delivered at the First Affiliated Hospital of Shanxi Medical University from March 1, 2012 to July 30, 2014 were selected, and matched the control group among non-GDM pregnant women by age, gestational age and residential address, and 324 cases and 318 controls were finally included. DNA was extracted and genotyped, and min P test and unconditional logistic regression model were used to estimate the relationship between FTO gene polymorphism and GDM. Results: At gene level, we did not find the association between FTO and the risk of GDM (P>0.05). After adjusted for family history of diabetes, pre-pregnancy body mass index and multiple comparisons using false discovery rate method, unconditional logistic regression analysis showed that pregnant women who carried the rs11075995 TT genotype (OR=0.59, 95%CI: 0.35-0.89), rs3826169 GG genotype (OR=0.59, 95%CI: 0.35-0.88), and rs74245270 GA genotype (OR=0.69, 95%CI: 0.49-0.98), GA or AA genotype(OR=0.70, 95%CI: 0.50-0.97) had reduced risk of GDM. However, pregnant women who carried the rs74018601 GA genotype (OR=1.51, 95%CI: 1.07-2.12), GA or AA genotype (OR=1.46, 95%CI: 1.06-2.02), rs7205009 AA genotype (OR=1.83, 95%CI: 1.18-2.86), GA or AA genotype (OR=1.53, 95%CI: 1.08-2.19), and rs9888758 AG genotype (OR=1.43, 95%CI: 1.02-2.00) had elevated risk of GDM. Conclusion: The polymorphisms of FTO gene rs11075995,rs3826169, rs74245270, rs74018601, rs7205009 and rs9888758 were associated with the risk of GDM.

Association of FTO common variant (rs9939609) with body fat in Turkish individuals

BackgroundVariations in the fat mass and obesity-associated (FTO) gene (16q12.2) are associated with obesity in some populations. This study aimed to determine the relationship between FTO gene polymorphism and adiposity&related markers in Turkish adults was aimed.MethodsThe present study included 200 participants aged 18–65 years, who were genotyped for variants of the FTO gene (rs9939609). Anthropometric measurements were performed. Body compositions were analyzed with Tanita BC 545 N Inner ScanTM. Infrared analyzer (VISCANTM) was also used to determinate the degree of abdominal fat. Body mass index (BMI), body adiposity index (BAI) and lipid accumulation products (LAP) index which are used in body fat estimation were calculated. Body fat amounts were classified using gender-based cut-offs. Odds ratio (OR) and 95% confidence interval (CI) were calculated to determine the risk of having a high body fat amount associated with the risk allele.ResultsThe frequency of the rs9939609 AA genotype was 19.0%, which was 42.5% for the AT genotype and 38.5% for the TT genotype (wild type). AA genotype was found to be higher in females than in males (26.0 and 12.0%, respectively). The total body fat amount of the individuals with AA genotype was high (28.5 ± 9.25%) compared to AT (27.0 ± 10.31%) and TT (23.7 ± 10.62%) genotype (p < 0.05). However, there was no difference in abdominal fat amounts (%) (AA:38.6%, AT:36.2%, TT:33.7%), internal fat levels and waist/hip ratios (p > 0.05). Significance of association between FTO genotypes and total body fat (%) was retained after adjustment for BMI and gender as well. BMI, LAP, and BAI index values were not different between different genotypes in all individuals and different genders (p > 0.05).ConclusionOur study supports that the FTO rs9939609 polymorphism is associated with fat accumulation in the whole body without being associated with abdominal fat accumulation in Turkish adults.

FTO gene polymorphisms and obesity risk in Chinese population: a meta-analysis.

There is tremendous increase in obesity worldwide. Many factors including diet, life style, genetic, and epigenetic changes contribute to obesity. The fat mass and obesity-associated (FTO) gene polymorphisms are strongly associated with obesity. It has been reported that FTO single-nucleotidepolymorphisms (SNPs) are associated with obesity in European populations; however, it was controversial in Chinese population. The present meta-analysis study was designed to investigate the association between FTO polymorphisms and obesity risk in Chinese population. The investigators searched studies using the following databases: PubMed, web of science, and Cochrane Central Register of Controlled Trials. A random-effects model was used to calculate the pooled odds ratios (ORs). The heterogeneity among the studies was measured by I2 value. Subgroup analysis was used to find out the potential factors influencing the heterogeneity. A total of 18 articles including 26 studies were included in the present meta-analysis. Overall, the FTO SNPs were significantly associated with obesity in Chinese population (OR 1.30; 95% CI 1.19-1.42; P < 0.001) under per-allele comparison. The subgroup analysis also showed strong association between four FTO SNPs (rs9939609, rs6499640, rs8050136, and rs1558902) and obesity risk. Furthermore, subgroup analysis stratified by children/adolescent and adult groups showed same trend. The present meta-analysis indicated that FTO SNPs are associated with obesity risk in both children/adolescents and adults in Chinese population.

Combined effect of FTO and MC4R gene polymorphisms on obesity in children and adolescents in Northwest China: a case-control study.

Fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes associated with obesity have been identified through Genome-wide Association Studies. However, no multiple loci interaction studies have been conducted in the Chinese population. This study investigated whether the combined effects of FTO and MC4R increase the risk of obesity in children and adolescents living in Northwest China. A total of 370 subjects (170 overweight/obese and 200 normal BMI subjects according to the Working Group on Obesity in China criteria) were enrolled using the random sampling method. FTO rs9939609 and rs9935401 and MC4R rs12970134 and rs17782313 interactions were analysed through generalized multifactor dimensionality reduction, and logistic regression models were used to calculate the risk of the relationship between genotypes and obesity. Generalized multifactor dimensionality reduction analysis showed a significant gene-gene interaction among FTO rs9939609/MC4R rs12970134/MC4R rs17782313, with a score of 10/10 for the cross-validation consistency and 9 for the sign test (p=0.011). A 2.453-fold increased risk of obesity was observed in individuals carrying the genotypes of FTO rs9939609 TA/AA, MC4R rs12970134 GA/AA, and MC4R rs17782313 TC/CC (adjusted for age, sex, and ethnicity; 95% CI=1.12-5.37, p=0.025). Our results suggested that FTO rs9939609, MC4R rs12970134, and MC4R rs17782313 are strongly associated with obesity. The combined effects were highly significant on obesity in children and adolescents living in Northwest China.

Relationship Between Fat Mass and Obesity-Associated (FTO) Gene Polymorphisms with Obesity and Metabolic Syndrome in Ethnic Mongolians.

BackgroundThe distribution of fat mass and obesity-associated gene (FTO) genes rs9939609 and rs1421085 in obese and normal ethnic Mongolians was analyzed to investigate the association of FTO gene polymorphisms with obesity and metabolic syndrome in ethnic Mongolians.Material/MethodsThe genotypes of FTO genes rs9939609 and rs1421085 in 500 subjects were detected by allele-specific PCR (AS-PCR). General characteristics and clinical biochemical indicators were compared between the obesity group and the control group. The correlation between different genotypes and obesity metabolic index was also analyzed.ResultsBody mass, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), SBP, DBP, FPG, triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were higher, while HDL-C was lower in the obesity group compared with controls. The frequencies of TT genotype and T allele in the obesity group were higher than those in the control group. The frequencies of these 3 genotypes and allele frequencies of Rs1421085 were comparable between the 2 groups (P>0.05). The risk of obesity in Mongolian individuals carrying rs9939609 AT genotype was 1.312 times higher and the risk in those carrying AA genotype was 1.896 times higher than in individuals with TT genotype. The body weight, BMI, WC, HC, and WHR in individuals with rs9939609 AA and AT genotypes were significantly higher than in those with TT genotype.ConclusionsThe AT/AA genotype and allele A of rs9939609 are associated with an increased risk of obesity.

A complete linkage disequilibrium in a haplotype of three SNPs in Fat Mass and Obesity associated (FTO) gene was strongly associated with anthropometric indices after controlling for calorie intake and physical activity

BackgroundThe underlying mechanism of the effect of FTO genotype on body mass index (BMI) and body composition is unknown. The objective of the study was to investigate the association of FTO gene polymorphisms with anthropometric indices in adolescent boys after adjustments for dietary intake and physical activity.MethodsIn this school-based study, we enrolled 123 male adolescents without extra weight and 110 male adolescents with body mass index (BMI) higher than + 1 Z-score. The DNA samples were genotyped for the FTO gene polymorphisms by DNA Sequencing. BMI and body composition were assessed using bioelectrical impedance analyzer scale. Association of the FTO polymorphisms with Weight, height, BMI, body fat percent and skeletal muscle percent were investigated. Data on potential confounders (calorie intake and physical activity) were collected through the use of pre-tested questionnaires.ResultsAdolescents with higher BMI and body fat percent and lower skeletal muscle percent were more likely to have a newly found haplotype of rs9930506, rs9930501 & rs9932754 (GGT) in the first intron of the FTO with complete linkage disequilibrium (LD) compared with those with the lower BMI (6.15;2.28–16.63), body fat percent (9.54;0.92–47.44) and higher skeletal muscle percent (9.26;1.85–46.38). This association was not changed after controlling for age. Additional adjustments for calorie intake and physical activity did not alter the association.ConclusionsA haplotype in the first intron of the FTO gene had a strong association with obesity indices in adolescent boys after adjustments for calorie intake and physical activity. It’s suggested that the FTO genotype exert its effects on adolescents’ anthropometric indices as haplotype and through mechanisms other than changes in calorie intake and expenditure.Trial registrationThis paper reports the first phase of a comprehensive interventional study (Interactions of Genetics, lifestyle and anthropometrics study or IGLA study) and is retrospectively registered in the Iranian Registry of Clinical Trials as IRCT2016020925699N2. Date registered: April 24, 2016. (http://www.irct.ir/searchresult.php?id=25699&number=2).

FTO rs9939609 Gene Polymorphism and Obesity: Lack of Association in Kidney Transplantation

The fat mass and obesity-associated (FTO) gene is one of the most important obesity susceptibility genes. Some FTO gene polymorphisms have been associated with obesity, diabetes, and hypertension, all conditions for which, after transplant, there is increased susceptibility, due to effects of immunosuppressive regimens. To evaluate whether FTO could be a candidate for targeted preventive intervention in the transplant setting, we investigated whether the common genetic variation, FTO rs9939609T>A, could affect weight gain and risk of cardiovascular complications in kidney transplantation. MethodsIn 198 kidney transplant recipients, FTO rs9939609 was investigated in association with body mass index (BMI)/obesity and with other clinical markers of posttransplant risk, then monitored up to 5 years after transplantation. Genotyping was performed using an allelic discrimination method on a real-time polymerase chain (PCR) system. Associations were analyzed using the chi-square test; differences between genotypes were examined with analysis of variance or Kruskal-Wallis test; tests for repeated measures and a general linear model analysis controlling for age and gender were also utilized. ResultsAllele and genotype frequencies of FTO rs9939609 in recipients (T/T, 29.8%; T/A, 49.0%; A/A, 21.2%; A, 45.7%; T, 54.3%) reflect those present in healthy Caucasian populations. In the face of pre-/posttransplant differences in total cholesterol, triglycerides, or fasting glucose, results did not show significant changes in these factors among genotypes either before or after transplantation. ConclusionThis study highlights a lack of association of FTO rs9939609T>A genotypes and posttransplant weight gain, plasma lipids, and fasting blood glucose in kidney transplantation.

Analysis of the Impact of Common Polymorphisms of theFTOandMC4RGenes with the Risk of Severe Obesity in Saudi Arabian Population

Obesity has reached epidemic proportions worldwide resulting in a serious public health problem. In Saudi Arabia, 28.7% of the population is obese due largely to the adoption of western dietary patterns over the last decade. The fat-mass and obesity associated (FTO) and melanocortin-4 receptor (MC4R) genes are ubiquitously expressed in the brain and pancreatic islets, and are the main link between the central nervous system and energy homeostasis based on food intake and energy expenditure. Genetic variants in the FTO and MC4R genes have been strongly associated with an increased obesity risk. To identify novel mutations in the MC4R gene and to perform correlation analyses of the known variants rs9939609 and rs1421085 in the FTO gene and rs17782313 near the MC4R gene in an obese Saudi population. A total of 136 obese patients and 104 healthy controls from King Fahd Hospital, Al-Khobar, were genotyped for single-nucleotide polymorphisms within or near the FTO and MC4R genes using the TaqMan assay. Leptin levels were determined by enzyme-linked immunosorbent assay. Targeted sequencing of MC4R exon was done by Sanger sequencing method. The study included 58 obese males and 78 obese females with a mean age of 39.78 ± 12.77 years and a mean body mass index (BMI) of 42.65 ± 9.03 kg/m2. A significant increase in the levels of leptin and triglycerides was associated with an increase of BMI. Other factors such as lactate dehydrogenase, gamma-glutamyltransferase, and high-density lipoprotein were also significantly higher in the severely obese cohort. The FTO polymorphisms were associated with a significantly increased risk for obesity and in BMI-stratified cohort, rs9939609 (T/A: odds ratio [OR] = 1.73, p = 0.007) and rs1421085 (T/C: OR = 1.56, p = 0.03) showed even stronger association. Genotyping for the near MC4R polymorphism, rs17782313 revealed an association with moderately obese patients (T/C: OR = 1.73, p = 0.038). The studied FTO gene polymorphisms were found to be significantly associated with increased BMI and were highly significantly associated with severe obesity. These FTO gene polymorphisms combined with a high-fat diet appear to promote early-onset obesity in the Saudi population. FTO polymorphisms appear to be universally associated with the risk of obesity, and further investigation into this genetic locus may provide clues for potential therapeutic targets.