FTO Single Nucleotide Polymorphisms Research Articles

The Impact of Haplotypes of the FTO Gene, Lifestyle, and Dietary Patterns on BMI and Metabolic Syndrome in Polish Young Adult Men.

Variants in fat mass and the obesity-associated protein (FTO) gene have long been recognized as the most significant genetic predictors of body fat mass and obesity. Nevertheless, despite the overall evidence, there are conflicting reports regarding the correlation between different polymorphisms of the FTO gene and body mass index (BMI). Additionally, it is unclear whether FTO influences metabolic syndrome (MetS) through mechanisms other than BMI's impact. In this work, we aimed to analyze the impact of the following FTO polymorphisms on the BMI as well as MetS components in a population of young adult men. The patient group consisted of 279 Polish young adult men aged 28.92 (4.28) recruited for the MAGNETIC trial. The single-nucleotide polymorphisms (SNPs), located in the first intron of the FTO gene, were genotyped, and the results were used to identify "protective" and "risk" haplotypes and diplotypes based on the literature data. Laboratory, as well as anthropometric measurements regarding MetS, were performed. Measured MetS components included those used in the definition in accordance with the current guidelines. Data regarding dietary patterns were also collected, and principal components of the dietary patterns were identified. No statistically significant correlations were identified between the analyzed FTO diplotypes and BMI (p = 0.53) or other MetS components (waist circumference p = 0.55; triglycerides p = 0.72; HDL cholesterol p = 0.33; blood glucose p = 0.20; systolic blood pressure p = 0.06; diastolic blood pressure p = 0.21). Stratification by the level of physical activity or adherence to the dietary patterns also did not result in any statistically significant result. Some studies have shown that FTO SNPs such as rs1421085, rs1121980, rs8050136, rs9939609, and rs9930506 have an impact on the BMI or other MetS components; nevertheless, this was not replicated in this study of Polish young adult males.

Type 2 diabetes linked FTO gene variant rs8050136 is significantly associated with gravidity in gestational diabetes in a sample of Bangladeshi women: Meta-analysis and case-control study.

Gestational diabetes mellitus (GDM) is a growing public health concern that has not been extensively studied. Numerous studies have indicated that a variant (rs8050136) of the fat mass-associated gene, FTO, is associated with both GDM and Type 2 diabetes mellitus(T2DM). We conducted a meta-analysis on the association between the FTO single nucleotide polymorphism (SNP) rs8050136 and T2DM, followed by a case-control study on the association of the said SNP and GDM in a sample of Bangladeshi women. A total of 25 studies were selected after exploring various databases and search engines, which were assessed using the Newcastle-Ottawa Scale (NOS). The MetaGenyo web tool was used to conduct this meta-analysis. A case-control study was performed on 218 GDM patients and 284 controls to observe any association between FTO rs8050136 and GDM. Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS) method, and statistical analyses were performed using various statistical softwares. In the meta-analysis 26231 cases and 43839 controls were examined. Pooled association analyses revealed a statistically significant relationship between the FTO rs8050136 polymorphism and an elevated risk of T2DM under all genetic models (P<0.05). In the case-control study, synergistic analyses of the SNP and gravida with GDM revealed a significant (P<0.01) association with an increase in odds by 1.6 to 2.4 folds in multigravida and decrease in odds by 2 folds in primigravida. A positive family history of diabetes and the minor allele of this SNP collectively increased the risk of developing GDM by many-fold (1.8 to 2.7 folds). However, after accounting for family history of diabetes and gravidity, analyses showed no significant association with GDM. Our meta-analysis revealed a significant association between SNP rs8050136 of FTO with T2DM, and this variant was substantially associated with an increased risk of GDM in a sample of Bangladeshi multigravida women.

Interaction of common variants of FTO gene and Dietary Inflammatory Index on obesity measures: Tehran Lipid and Glucose Study

BackgroundThis study aimed to examine the interaction of Dietary Inflammatory Index (DII) and fat mass and obesity-associated gene (FTO) single-nucleotide polymorphisms (SNPs) on change in obesity measures.MethodsA total of 4480...

Association of the Gene FTO Single Nucleotide Polymorphism, rs9939609 with Type 2 Diabetes Mellitus in Pakistani Cohort

To date, inconclusive data is available about the insight of the FTO gene variant with type 2 diabetes mellitus. T2DM is a chronic disease and a rising problem worldwide. Its complications lead to an increase in the burden of mortality specifically in lower and medium-income countries. Genome-wide association studies have spotted many genetic loci that are related to T2DM and validate the complicated polygenic traits. Many variants of different genes including FTO are associated with T2DM hence, this study was designed to inspect and unfold obscure data in South Asians. The main objective of present study is to identify the relation of FTO intronic variant rs9939609 with T2DM in Karachi-based Sindhi population of Pakistan. Total recruited individuals were grouped as diabetic cases and controls. Out of the total recruited subjects, genotyping was done on 152 samples using T-ARMS PCR however, demographic and clinical data were recorded of all individuals. The results showed that the frequency of variant genotypes in the diabetic case group was 11 % for AA, 45 % for AT and 44 % for TT though, the frequency of the lethal allele (T) was 34 %. These outcomes concluded, rare T allele frequency is higher among diabetic cases as compared to controls and provides the contribution from the Pakistani population to support the previous controversial findings. This study concluded FTO gene-single nucleotide polymorphism, rs9939609 is associated with T2DM but still, it is a growing need to do further studies on T2DM susceptible genes with different polymorphisms to recognize targets in the field of pharmacogenomics for clinical implementation.

Minor alleles in the FTO SNPs contributed to the increased risk of obesity among Korean adults: meta-analysis from nationwide big data-based studies.

Many studies have revealed an association between fat mass and the obesity-related gene (FTO) and obesity. On the other hand, no meta-analysis was conducted with data from only Koreans. Therefore, this study performed a meta-analysis using Korean data to provide evidence for the association between FTO single nucleotide polymorphisms (SNPs) and the risk of obesity among Korean adults. Meta-analysis was finally conducted with data extracted from seven datasets of four studies performed on Korean adults after the screening passed. Five kinds of FTO SNPs (rs9939609, rs7193144, rs9940128, rs8050136, and rs9926289) were included, and the relationship between FTO SNPs and body mass index (BMI) was investigated using linear regression with an additive model adjusted for covariants, such as age, sex, and area. The minor alleles of FTO SNPs were associated with increased BMI (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.21-1.42). In sub-group analysis, FTO rs9939609 T>A was significantly associated with BMI (OR, 1.23; 95% CI, 1.06-1.42). The other FTO SNPs together were significantly associated with BMI (OR, 1.37; 95% CI, 1.25-1.49). The publication bias was not observed based on Egger's test. This meta-analysis showed that minor alleles in the FTO SNPs were significantly associated with an increased BMI among Korean adults. This meta-analysis is the first to demonstrate that minor alleles in the FTO SNPs contribute significantly to the increased risk of obesity among Korean adults using data from a Korean population.

FTO and Anthropometrics: The Role of Modifiable Factors.

Numerous gene variants are linked to an individual’s propensity to become overweight or obese. The most commonly studied gene variant is the FTO single nucleotide polymorphism. The FTO risk allele is linked with increased body mass, BMI and other lifestyle factors that may perpetuate an individual’s risk for obesity. Studies assessing eating behaviors, eating preferences, nutrition interventions and other lifestyle factors were reviewed. These studies demonstrated a clear difference in eating behaviors and preferences. Lifestyle modifications including physical activity and diet were effective in weight management even in those with the risk allele.

FTO Common Obesity SNPs Interact with Actionable Environmental Factors: Physical Activity, Sugar-Sweetened Beverages and Wine Consumption.

Genetic background is estimated to play >50% in common obesity etiology. FTO single nucleotide polymorphisms (SNPs) are strongly associated with BMI, typically in European cohorts. We investigated the interaction of common FTO SNPs with actionable environmental factors, namely physical activity, sugar-sweetened beverages (SSB) and wine consumption, and verified FTO common SNPs predisposition to obesity in the Israeli population. Adults’ (>18 years old, n = 1720) FTO common SNPs data and lifestyle and nutrition habits questionnaires were analyzed using binary logistic regression models, adjusted for confounding variables (age, sex) assuming dominant, recessive and additive genetic models. Eighteen FTO SNPs were associated with significant increased obesity risk and interacted with physical activity (p < 0.001), wine consumption (p < 0.014) and SSB consumption (p < 0.01). Inactive rs9939609 risk-allele carriers had significantly higher obesity risk compared to their active counterparts (OR = 2.54, 95% CI 1.91–3.39 and OR = 3.77, 95% CI 2.47–5.75; p < 0.001 with 3.1 and 3.5 BMI increment for heterozygotes and homozygotes, respectively). SSB consumption (≥1 serving/day) significantly raised obesity risk and wine consumption (1–3 drinks/weekly) significantly lowered obesity risk for rs9939609 risk-allele carriers (OR = 1.54, 95% CI 1.05–2.27; p = 0.028 and OR = 0.61, 95% CI 0.47–0.79; p < 0.001, respectively). Our findings demonstrate that actionable lifestyle factors modify the common FTO obesity risk in predisposed carriers, and they have personal and public health implications.

Association of FTO, ABCA1, ADRB3, and PPARG variants with obesity, type 2 diabetes, and metabolic syndrome in a Northwest Mexican adult population

To identify associations among allelic variants of the genes FTO, ABCA1, ADRB3, and PPARG with anthropometric and biochemical traits, metabolic diseases (obesity, T2D or metabolic syndrome) in an adult population from Northwest Mexico. Blood samples were collected from 846 subjects including 266 normal weight subjects, 285 with obesity, and 295 with T2D. Of the 846 persons in the study, 365 presented metabolic syndrome diagnostic criteria. Anthropometric and biochemical traits were recorded and 4 single nucleotide polymorphisms (SNPs): FTO rs9939609 A-allele, ABCA1 rs9282541 A-allele, ADRB3 rs4994 G-allele, and PPARG rs1801282 G-allele were genotyped by real-time PCR. FTO rs9939609 A-allele was significantly associated with obesity (p: 8.3×10-4), and metabolic syndrome (p: 0.001), but no individual SNPs were significantly associated with T2D. Finally, the cumulative risk of the four SNPs was significantly associated with obesity (p: 1.95×10-4). Associations in FTO, ABCA, ADRB3, and PPARG SNPs presented in this study with obesity and metabolic syndrome could represent a risk for developing metabolic diseases in Northwest Mexican adult subjects.

Association between the FTO SNP rs9939609 and Metabolic Syndrome in Chilean Children.

Background: The increasing prevalence of obesity in children has raised the incidence of Metabolic Syndrome (MetS) in this age group. Given the short- and long-term health impact of MetS, it is essential to prevent its onset by detecting its main triggers. Besides, genetic factors play an essential role in influencing which individuals within a population are most likely to develop obesity in response to a particular environment. In this regard, a common variation in the FTO gene is reproducibly associated with BMI and obesity from childhood and the genetic load has been linked to several cardiovascular risk factors, highlighting the FTO single nucleotide polymorphism (SNP) rs9939609. Therefore, this study aimed to establish the relationship between the FTO SNP rs9939609 and MetS. Methods: A cross-sectional study was carried out on 220 children from the Biobío region (Chile). MetS diagnosis was established through the modified Cook criteria, using prevalence ratios, COR curves, and linear regressions to determine its association with MetS and its components. Results: The prevalence of MetS was significantly increased among carriers of the risk allele (A): TT, 20.2%; TA, 25.4%; AA, 44.7% (p = 0.006). Also, the presence of A was associated with altered MetS-related variables. Conclusions: The FTO SNP rs9939609 was associated with a raised prevalence of MetS among A allele carriers, and was higher in the homozygous genotype (AA).

The Potential Role of N6-Methyladenosine (m6A) Demethylase Fat Mass and Obesity-Associated Gene (FTO) in Human Cancers.

N6-methyladenosine (m6A) demethylase fat mass and obesity-associated gene(FTO), previously recognized to be related with obesity and diabetes, was gradually discovered to be dysregulated in multiple cancers and plays an oncogenic or tumor-suppressive role. However, the specific expression and pro- or anti-cancer role of FTO in various cancers remained controversial. In this review, through summarizing the available literature, we found that FTO single nucleotide polymorphisms (SNPs) were closely related with cancer risk. Additionally, the dysregulation of FTO was implicated in multiple biological processes, such as cancer cell apoptosis, proliferation, migration, invasion, metastasis, cell-cycle, differentiation, stem cell self-renewal and so on. These modulations mostly relied on the communications between FTO and specific signaling pathways, including PI3K/AKT, MAPK and mTOR signaling pathways. Furthermore, FTO had great potential for clinical application by serving as a prognostic biomarker.

Association study of candidate genes with obesity and metabolic traits in antipsychotic-treated patients with first-episode psychosis over a 2-year period.

Patients with a first episode of psychosis (FEP) often display different metabolic disturbances even independently of drug therapy. However, antipsychotic (AP) treatment, especially with second-generation APs, is strongly linked to weight gain, which increases patients' risk of developing obesity and other metabolic diseases. There is an important genetic risk component that can contribute to the appearance of these disturbances. The aim of the present study was to evaluate the effect of polymorphisms in selected candidate genes on obesity and other anthropometric and metabolic traits in 320 AP-treated FEP patients over the course of a 2-year follow-up. These patients were recruited in the multicentre PEPs study (Phenotype-genotype and environmental interaction; Application of a predictive model in first psychotic episodes). A total of 127 validated single nucleotide polymorphisms (SNPs) in 18 candidate genes were included in the genetic analysis. After Bonferroni correction, SNPs in ADRA2A, FTO, CNR1, DRD2, DRD3, LEPR and BDNF were associated with obesity, abdominal circumference, triglycerides, HDL cholesterol, and/or percentage of glycated haemoglobin. Although our results should be interpreted as exploratory, they support previous evidence of the impact of these candidate genes on obesity and metabolic status. Further research is required to gain a better knowledge of the genetic variants that can be considered relevant metabolic risk factors. The ability to identify FEP patients at higher risk for these metabolic disturbances would enable clinicians to better select and control their AP treatment.

Evidence for the association between FTO gene variants and vitamin B12 concentrations in an Asian Indian population

BackgroundLow vitamin B12 concentrations have been associated with major clinical outcomes, including adiposity, in Indian populations. The Fat mass and obesity-associated gene (FTO) is an established obesity-susceptibility locus; however, it remains unknown whether it influences vitamin B12 status. Hence, we investigated the association of two previously studied FTO polymorphisms with vitamin B12 concentrations and metabolic disease-related outcomes and examined whether these associations were modified by dietary factors and physical activity.MethodsA total of 176 individuals with type 2 diabetes, 152 with pre-diabetes, and 220 normal glucose-tolerant individuals were randomly selected from the Chennai Urban Rural Epidemiology Study. Anthropometric, clinical, and biochemical investigations, which included body mass index (BMI), waist circumference, vitamin B12, homocysteine, and folic acid were measured. A validated food frequency questionnaire was used for dietary assessment and self-reported physical activity measures were collected. An unweighted genetic risk score (GRS) was calculated for two FTO single-nucleotide polymorphisms (rs8050136 and rs2388405) by summation of the number of risk alleles for obesity. Interaction analyses were performed by including the interaction terms in the regression model.ResultsThe GRS was significantly associated with increased BMI (P = 0.009) and risk of obesity (P = 0.023). Individuals carrying more than one risk allele for the GRS had 13.13% lower vitamin B12 concentrations, compared to individuals carrying zero risk alleles (P = 0.018). No associations between the GRS and folic acid and homocysteine concentrations were observed. Furthermore, no statistically significant GRS-diet or GRS-physical activity interactions with vitamin B12, folic acid, homocysteine or metabolic-disease outcomes were observed.ConclusionThe study shows for the first time that a genetic risk score using two FTO SNPs is associated with lower vitamin B12 concentrations; however, we did not identify any evidence for the influence of lifestyle factors on this association. Further replication studies in larger cohorts are warranted to investigate the association between the GRS and vitamin B12 concentrations.

The association of the common fat mass and obesity associated gene polymorphisms with type 2 diabetes in obese Iraqi population

Background & objectivesThis study investigates the association of two potential Fat mass and obesity associated gene (FTO) gene polymorphisms (rs9939609 and rs918031) as potential predictors of type 2 diabetes (T2D) in obese Iraqi population and their metabolic effects on hyperglycemia and insulin sensitivity. Materials & methodsThe study included 400 participants with obesity & T2D, with a matching 400 obese non-diabetic cohort. Venous blood samples were collected for DNA extraction. Using specific primers and restriction enzymes, genotyping was performed to identify the various alleles for each gene. The genotype and allele frequencies determined by multinomial logistic regression analysis for FTO single nucleotide polymorphisms (rs9939609) among all the study groups. ResultsThere is a two-fold increase in the risk of T2D within the homozygous genotype (TT) group (OR = 2.43, CI 95% 3.57–11.2, P ≤ 0.001) as compared to the wild type (TA). In addition, there was a significantly higher level of the minor allele genotype (T) in T2D patients when compared to the control group, (P ≤ 0.001). ConclusionWe conclude that the FTO rs9939609 genotype significantly affect the development of insulin resistance, therefore the future occurrence of T2D, in obese individuals.

Assessment of the FTO gene polymorphisms (rs1421085, rs17817449 and rs9939609) in exercise-trained men and women: the effects of a 4-week hypocaloric diet

BackgroundVariations in the fat mass and obesity-associated gene (FTO) are associated with obesity; however, it is unclear if changes in energy intake affect the adaptive response to caloric restriction in those with risk variants. The three FTO single nucleotide polymorphisms (SNPs), rs1421085, rs17817449 and rs9939609, are in strong linkage disequilibrium. Thus, the purpose of this investigation was to determine the role of these FTO SNPs vis-à-vis the effects of a 4-week hypocaloric diet on body composition in exercise-trained men and women. Two salivary biomarkers that associate with energy expenditure were also assessed (cortisol and salivary alpha-amylase, sAA).MethodsForty-seven exercise-trained men (n = 11) and women (n = 36) (mean ± SD: age 32 ± 9 years; height 169 ± 8 cm, body mass index 24.5 ± 2.9 kg/m2, hours of aerobic training per week 4.9 ± 3.8, hours of weight training per week 3.9 ± 2.4, years of training experience 13.4 ± 7.0) completed a 4-week hypocaloric diet (i.e., decrease total calories by ~ 20–25% while maintaining a protein intake of ~ 2.0 g/kg/d). Subjects were instructed to maintain the same training regimen and to decrease energy intake via carbohydrate and/or fat restriction during the treatment period. Body composition was assessed via dual-energy X-ray absorptiometry (DXA) (Model: Hologic Horizon W; Hologic Inc., Danbury CT USA). Total body water was determined via a multifrequency bioelectrical impedance (BIA) device (InBody 770). Saliva samples were collected pre and post intervention in order to genotype the participants as well as to determine the concentrations of cortisol and sAA.ResultsOf the 47 subjects, 15 were of normal risk for obesity whereas 32 were carriers of the FTO gene risk alleles. Subjects were grouped based on their genotype for the three FTO SNPs (i.e., rs1421085, rs17817449 and rs9939609) due to their strong linkage disequilibrium. We have classified those with the normal obesity risk as “non-risk allele” versus those that carry the “risk allele” (i.e., both heterozygous and homozygous). Both groups experienced a significant decrease in total energy intake (p < 0.01); non-risk allele: pre kcal 2081 ± 618, post kcal 1703 ± 495; risk allele: pre kcal 1886 ± 515, post kcal 1502 ± 366). Both groups lost a significant amount of body weight (p < 0.01); however, there was no difference between groups for the change (post minus pre) in each group (risk allele change: − 1.0 ± 1.2 kg, non-risk allele change: − 1.2 ± 1.4 kg). Additionally, both groups lost a significant amount of fat mass (p < 0.01) with no differences between groups for the change in fat mass (risk allele change for fat mass: 1.1 ± 0.7 kg, non-risk allele change − 0.9 ± 0.4 kg). There were no significant changes in either group for fat free mass or total body water. The change in salivary alpha-amylase or cortisol was not different between groups.ConclusionsIn the short-term (i.e., 4 weeks), exercise-trained men and women consuming a hypocaloric diet that is relatively high in protein experience similar changes in body composition due exclusively to a decrement in fat mass and independent of FTO allele status. Therefore, weight and fat loss on a hypocaloric diet is, at least in the short-term, unaffected by the FTO gene.

Sexual Dimorphism of a Genetic Risk Score for Obesity and Related Traits among Chinese Patients with Type 2 Diabetes

Background: Obesity is more prevalent in men than in women in China, especially within the middle-aged population. Objectives: The present study aims to determine the contribution of sexual dimorphisms to obesity and related traits in terms of the mechanisms involving the obesity-related genetic variants among patients of Chinese Han ancestry with type 2 diabetes. Method: In the Chinese National Diabetes and Metabolic Disorders Study, 2,555 out of 4,036 patients with type 2 diabetes were treatment naive, including 1,142 men and 1,413 women. Single-nucleotide polymorphisms (SNP) from 18 genomic loci previously found to be associated with obesity-related traits were successfully genotyped, and a genetic risk score (GRS) was constructed by summing the risk alleles for obesity. Results: Single SNP analysis showed that genetic variants in SLC30A10, TMEM18, GNPDA2, PRL, TFAP2B, BDNF, MTCH2, FTO, and MC4R were nominally associated with waist circumference (WC), BMI, and risk for abdominal or general obesity in the untreated patients with type 2 diabetes, as well as in the total group of patients with type 2 diabetes (untreated and treated) (p < 0.05). Interactions between sex and SNP in PRL, MTCH2,and FTO were detected (p < 0.05). In the untreated patients with diabetes, the GRS was nominally associated with WC (β = 0.0032, SE = 0.0011; p = 0.003), BMI (β = 0.0030, SE = 0.0013; p = 0.027), and increased risk for abdominal (OR = 1.08; 95% CI 1.02–1.13; p = 0.004) or general obesity (OR = 1.07; 95% CI 1.02–1.13; p = 0.011) in men but not in women. GRS-sex interactions were detected in the determinant of WC (p = 0.019) and abdominal obesity (p = 0.016). Among patients aged 30–60 years, GRS was found to be significantly associated with WC (β = 0.0050, SE = 0.0016; p = 0.002) and abdominal obesity (OR = 1.10; 95% CI 1.04–1.17; p = 0.001) and nominally associated with BMI (β = 0.0057, SE = 0.0020; p = 0.005) and general obesity (OR = 1.07; 95% CI 1.01–1.14; p = 0.027) in men, whereas in women none of the associations were detected. GRS-sex interactions were present in the determinant of WC (p = 0.015), BMI (p = 0.032), and abdominal obesity (p = 0.012). Among patients aged 60 years or older, neither an association of GRS with obesity-related traits nor GRS-sex interactions were detected. Conclusions: Genetic factors contribute to obesity-related traits in a sex-dependent pattern among middle-aged Chinese, and men tend to be more susceptible to the genetic risk of obesity.

Familial aggregation and linkage analysis with covariates for metabolic syndrome risk factors

BackgroundMechanisms of metabolic syndrome (MetS) causation are complex, genetic and environmental factors are important factors for the pathogenesis of MetS In this study, we aimed to evaluate familial and genetic influences on metabolic syndrome risk factor and also assess association between FTO (rs1558902 and rs7202116) and CETP(rs1864163) genes' single nucleotide polymorphisms (SNP) with low HDL_C in the Tehran Lipid and Glucose Study (TLGS). Materials and methodsThe design was a cross-sectional study of 1776 members of 227 randomly-ascertained families. Selected families contained at least one affected metabolic syndrome and at least two members of the family had suffered a loss of HDL_C according to ATP III criteria.In this study, after confirming the familial aggregation with intra-trait correlation coefficients (ICC) of Metabolic syndrome (MetS) and the quantitative lipid traits, the genetic linkage analysis of HDL_C was performed using conditional logistic method with adjusted sex and age. ResultsThe results of the aggregation analysis revealed a higher correlation between siblings than between parent-offspring pairs representing the role of genetic factors in MetS. In addition, the conditional logistic model with covariates showed that the linkage results between HDL_C and three marker, rs1558902, rs7202116 and rs1864163 were significant. ConclusionsIn summary, a high risk of MetS was found in siblings confirming the genetic influences of metabolic syndrome risk factor. Moreover, the power to detect linkage increases in the one parameter conditional logistic model regarding the use of age and sex as covariates.

Establishing a genetic link between FTO and VDR gene polymorphisms and obesity in the Emirati population

BackgroundObesity is a metabolic disease that is widely prevalent with approximately 600 million people classified as obese worldwide. Its etiology is multifactorial and involves a complex interplay between genes and the environment. Over the past few decades, obesity rates among the Emirati population have been increasing. The aim of this study was to investigate the association of candidate gene single nucleotide polymorphisms (SNPs), namely FTO (rs9939609) and VDR (rs1544410), with obesity in the UAE population.MethodsThis is a case-control study in which genomic DNA was extracted from saliva samples of 201 obese, 115 overweight, and 98 normal subjects in the United Arab Emirates (UAE). Genotyping for the variants was performed using TaqMan assay.ResultsThe mean Body Mass Index (BMI) ± SD for the obese, overweight, and normal subjects was 35.76 ± 4.54, 27.53 ± 1.45, and 22.69 ± 1.84 kg/m2, respectively. Increasing BMI values were associated with increase in values of HbA1c, systolic and diastolic blood pressure. There was a significant association observed between the FTO SNP rs9939609 and BMI (p = 0.028), with the minor allele A having a clear additive effect on BMI values. There was no significant association detected between BMI and rs1544410 of VDR. Moreover, significant interaction between the FTO rs9939609 and physical activity reduced the “AA” genotype effect on increase in BMI (p = 0.027).ConclusionsOur study findings indicate that the minor allele A of the rs9939609 has a significant association with increasing BMI values. Moreover, our findings support the fact that increasing BMI is associated with increasing risks of other comorbidities such as higher blood pressure, poorer glycemic control, and higher triglycerides. In addition, physical activity was found to attenuate the effect of the “AA” genotype on the predisposition to higher BMI values.

Gender-specific association of the rs6499640 polymorphism in the FTO gene with plasma lipid levels in Chinese children

The fat mass- and obesity-associated gene (FTO) is significantly associated with obesity, but the associations of FTO with obesity-related traits are not fully described. We aimed to investigate the association of the FTO single nucleotide polymorphism (SNP) rs6499640 with lipid levels in Chinese children. A total of 3503 children aged 6-18 years were included in the present study. Lipid levels were analyzed and the SNP rs6499640 was genotyped using the TaqMan Allelic Discrimination Assay. Statistically significant associations were found between rs6499640 and low-density lipoprotein cholesterol (LDL-C) (p = 0.008), total cholesterol (TC) (p = 0.005), and triglycerides (TG) (p < 0.001) in girls under a dominant model adjusted for age and BMI. No statistical significance was found between the SNP and lipid levels in boys. We demonstrated for the first time that the SNP rs6499640 in FTO is associated with LDL-C, TC, and TG in Chinese girls. Our study identified a new risk locus for lipid levels in children.

FTO affects food cravings and interacts with age to influence age-related decline in food cravings.

The fat mass and obesity associated gene (FTO) was the first gene identified by genome-wide association studies to correlate with higher body mass index (BMI) and increased odds of obesity. FTO remains the locus with the largest and most replicated effect on body weight, but the mechanism whereby FTO affects body weight and the development of obesity is not fully understood. Here we tested whether FTO is associated with differences in food cravings and a key aspect of dopamine function that has been hypothesized to influence food reward mechanisms. Moreover, as food cravings and dopamine function are known to decline with age, we explored effects of age on relations between FTO and food cravings and dopamine function. Seven-eight healthy subjects between 22 and 83years old completed the Food Cravings Questionnaire and underwent genotyping for FTO rs9939609, the first FTO single nucleotide polymorphism associated with obesity. Compared to TT homozygotes, individuals carrying the obesity-susceptible A allele had higher total food cravings, which correlated with higher BMI. Additionally, food cravings declined with age, but this age effect differed across variants of FTO rs9939609: while TT homozygotes showed the typical age-related decline in food cravings, there was no such decline among A carriers. All subjects were scanned with [18F]fallypride PET to assess a recent proposal that at the neurochemical level FTO alters dopamine D2-like receptor (DRD2) function to influence food reward related mechanisms. However, we observed no evidence of FTO effects on DRD2 availability.

Obesity candidate genes, gestational weight gain, and body weight changes in pregnant women.

To examine the associations of two obesity-associated genes, FTO (rs9939609) and GNB3 (rs5443) single nucleotide polymorphisms (SNPs), with early pregnancy body mass index, gestational weight gain, and postpartum weight retention. Secondary data analysis of self-identified white (n = 580) and black (n = 194) women who participated in a randomized controlled trial (2009-2014) and provided a saliva sample of DNA. Bivariate relationships were assessed using analysis of variance. Multiple regression models assessed the relationship between outcomes and gene SNPs, controlling for income, parity, and smoking status. FTO and GNB3 gene associations with pregnancy weight were different by racial group and early pregnancy body mass index. Obese black women homozygote for the FTO risk allele (AA) had a higher gestational weight gain compared with non-risk homozygotes (TT) (P = 0.006). GNB3 non-risk CC homozygotes tended to have a lower gestational weight gain compared with heterozygotes (P = 0.05). White GNB3 C carriers tended to be heavier in early pregnancy (P <0.1) and GNB3 homozygote (TT) overweight women tended to have lower postpartum weight retention than C carriers. The FTO gene and possibly the GNB3 gene are associated with high gestational weight gain in obese black women. Obese carriers of the FTO risk allele gained 4.1 kg (AT) and 7.6 kg (TT) more than those without risk alleles. Overweight GNB3 heterozygotes (CT) gained 6.6 kg less than homozygotes (CC). Overweight or obese black women who have either risk variant are at risk for high gestational weight gain.