SNP Rs9939609 Research Articles

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

Meta-regression of genome-wide association studies to estimate age-varying genetic effects

Fixed-effect meta-analysis has been used to summarize genetic effects on a phenotype across multiple Genome-Wide Association Studies (GWAS) assuming a common underlying genetic effect. Genetic effects may vary with age (or other characteristics), and not allowing for this in a GWAS might lead to bias. Meta-regression models between study heterogeneity and allows effect modification of the genetic effects to be explored. The aim of this study was to explore the use of meta-analysis and meta-regression for estimating age-varying genetic effects on phenotypes. With simulations we compared the performance of meta-regression to fixed-effect and random -effects meta-analyses in estimating (i) main genetic effects and (ii) age-varying genetic effects (SNP by age interactions) from multiple GWAS studies under a range of scenarios. We applied meta-regression on publicly available summary data to estimate the main and age-varying genetic effects of the FTO SNP rs9939609 on Body Mass Index (BMI). Fixed-effect and random-effects meta-analyses accurately estimated genetic effects when these did not change with age. Meta-regression accurately estimated both main genetic effects and age-varying genetic effects. When the number of studies or the age-diversity between studies was low, meta-regression had limited power. In the applied example, each additional minor allele (A) of rs9939609 was inversely associated with BMI at ages 0 to 3, and positively associated at ages 5.5 to 13. Our findings challenge the assumption that genetic effects are consistent across all ages and provide a method for exploring this. GWAS consortia should be encouraged to use meta-regression to explore age-varying genetic effects.

Association of an intronic SNP rs9939609 in FTO gene with type 2 diabetes mellitus among Bangladeshi population: A case–control study combined with updated meta-analysis

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder, caused by both genetic and environmental variables. The rs9939609 variant with a T > A mutation of the Fat mass obesity (FTO) gene has been known to have a strong association with T2DM and extensively investigated for its role in T2DM in different populations. In this study we conducted a case–control study based on the Bangladeshi population and a combined updated meta-analysis using the data of previous studies from different populations and our study to investigate the association of rs9939609 with T2DM. A total of 156 diabetic patients and 144 healthy non-diabetic controls were recruited. ARMS (Amplification Refractory Mutation System) PCR method was used for genotyping and sequencing was done to validate the PCR results. Our study found a significant association (p < 0.05) of rs9939609 with T2DM in co-dominant AA vs. TT (OR = 2.64) dominant TA + AA vs. TT (OR = 2.12) and additive 2(AA) + TA(OR = 2.224) genetic models. From the meta-analysis, we found significant association of rs9939609 with T2DM in the overall population for all genetic models. However, subgroup analysis showed negligible association in the Caucasian population unlike the Asian population. This is the first case–control study conducted on rs9939609 in the Bangladeshi population that revealed significant association with T2DM and also imply that the connection between them may be mediated by mechanisms other than obesity and increased BMI which was supported by results found in most of the Asian populations. This study could be used as a foundation for future association studies involving larger populations.

Association of FTO gene variant rs9939609 with hyperandrogenemia and fasting glucose\xa0levels in South Indian women with polycystic ovarian syndrome

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

Genetic Association of FTO rs9939609 Polymorphism with Hypertension in Pakistani Population

Background: Hypertension is a medical condition that often occurs parallel to diabetes and obesity. Previously, the role of fat mass and obesity associated (FTO) gene rs9939609 polymorphism (c.46-23525T&gt;A) with obesity has been reported while prevalence and etiological differences exist among different regions and ethnic groups. Aim: To investigate the association of FTO rs9939609 SNP with hypertension in Pakistani population. Study design: Cross-sectional study. Place and duration of study: Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan from 1st January 2019 to 31st December 2020. Methodology: One hundred and ten diagnosed hypertension patients along with 128 healthy volunteers were selected randomly. The single nucleotide polymorphism was analyzed using Amplified Refractory Mutation System-Polymerase Chain Reaction. Results: In hypertension patients, females were found to be relatively more affected and average blood pressure lies in stage 1. However, we found no significant difference in genotypic frequencies of FTO rs9939609; TT (22.6%), AA (39.6%) and AT (37.8%) and TT (17.18%), AA (39.06%), and AT (43.75%) among HT and controls, respectively. The p and OR values for risk type genotype (AA) are 0.4697 and 0.7700 (95% CI=0.3788-1.565), respectively. Subsequently, the high percentage (60.0 %) of risk genotype (AA) was found in obese-body mass index in hypertension patients. Conclusion: FTO rs9939609 single nucleotide polymorphism may not be a genetic risk factor associated with onset of hypertension directly and is linked with obesity in Pakistani patients. Keywords: FTO, Hypertension, Obesity, Pakistani patients, rs9939609

The Significance of the FTO Gene for Weight and Body Composition in Swedish Women With Severe Anorexia Nervosa During Intensive Nutrition Therapy

Objective: The aim of this prospective study was to investigate the potential influence of the fat mass and obesity-associated gene (FTO), SNP rs9939609, on body mass index (BMI) and body composition in women with anorexia nervosa (AN) undergoing intensive nutrition therapy. Method: Twenty-five female patients with AN (20.1 ± 2.3 years; BMI, 15.5 ± 0.9 kg/m2) were included for 12 weeks of treatment with a high-energy diet. FTO was genotyped and body composition parameters were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography at baseline and after 12 weeks. Results: The distribution of the different FTO genotypes were as follows: AA, 24%; TA, 48%; and TT, 28%. Patients gained a median of 9.8 kg (range, 5.5–17.0 kg) and BMI increased to 19.0 ± 0.9 kg/m2. The increase in BMI, fat mass, and the quotient fat/muscle area was significant for the TT and TA genotype groups. Total lean mass was stable in all genotype groups. We could not demonstrate any difference among the 3 FTO genotypes related to the increases in BMI during nutrition therapy when the additive, dominant, and recessive models of inheritance were applied. Conclusions: Irrespective of the FTO genotype, there was no difference in weight response during nutrition therapy. Hence, in this small study there was limited support for individualized nutrition therapy for AN based on FTO genotype.

The FTO, PNPLA3 and TM6SF2 Gene Polymorphisms and Genetic Predisposition to NAFLD in Yakut Population

The aim of our research was to study the distribution of alleles and genotypes of the FTO rs9939609 SNP, the PNPLA3 rs738409 SNP, and the TM6SF2 rs58542926 SNP in the Yakut population. Methods and Results: A total of 85 DNA samples from the population were tested. An analysis of the frequency distribution of alleles and genotypes of the FTO rs9939609 SNP in the study group did not reveal significant differences. An analysis of the frequency distribution of alleles and genotypes of the PNPLA3 rs738409 SNP revealed that in men and women the G allele and the homozygous GG genotype prevailed. The results of the analysis of the frequency distribution of alleles and genotypes of the TM6SF2 rs58542926 SNP showed the predominance of individuals with the C allele (89% in men and 90% in women) with statistical significance in women. Conclusion: The further studies with a larger sample size are required to detect the features of the distribution of alleles and genotypes of the FTO rs9939609 SNP and the TM6SF2 rs58542926 SNP in that population.

Abstract PS8-17: Assessing effect modification of obesity-associated genes variants in FTO, MC4R, BDNF, and CREB1 on weight loss among breast cancer survivors enrolled in the randomized lifestyle, exercise, and nutrition (LEAN) study

Abstract Background: Obesity is a leading risk factor for breast cancer in post-menopausal women and is associated with greater risk of recurrence and cancer-specific mortality. There are over 3 million female breast cancer survivors in the United States, and nearly 65% are either overweight or obese. Lifestyle intervention studies have been shown to be effective in achieving clinically meaningful weight loss for breast cancer survivors with a BMI &amp;gt; 25 kg/m2. However, individual variability in body weight response to diet or exercise interventions has been previously reported among carriers of common obesity-genetic variants. Our study examined whether common variants of obesity-associated genes FTO, MC4R, BDNF, and CREB moderated the effects of an exercise and nutrition intervention on weight change among breast cancer survivors. Methods: A total of 151 breast cancer survivors with a body mass index (BMI) ≥ 25 kg/m2 at baseline were randomly assigned to a 6-month weight loss intervention (n=93) or usual care group (n=58). The weight loss intervention included eleven 30-min counseling sessions on improving nutrition and increasing physical activity. Height, weight and body composition (via dual energy X-ray absorptiometry) were measured at baseline and six months. Genotyping of FTO rs9939609, MC4R rs6567160, BDNF rs11030104, CREB1 rs17203016 was performed using Taqman® SNP genotyping assays. Association analyses were performed in SAS version 9.4, separately for each SNP and assuming a dominant genetic model. Linear mixed models were used to analyze the main effects of genotype and the intervention on weight, BMI, and percent body fat changes at 6 months, with adjustment for age. Appropriate cross product terms were included in each regression model to analyze the potential interaction between genotype and treatment arm. All statistical tests were evaluated against a Bonferroni-corrected alpha of 0.0125. Results: The genetic distributions of the FTO SNP rs9939609, MC4R SNP rs6567160, BDNF SNP rs11030104, CREB1 SNP rs17203016 did not differ significantly by treatment arm. Changes in weight, BMI, and percent body fat did not differ significantly between carriers of the FTO SNP rs9939609, MC4R SNP rs6567160, BDNF SNP rs11030104, and CREB1 SNP rs17203016 risk alleles compared to non-carriers (p-interaction &amp;gt; 0.0125 for each SNP and across all outcomes). Women in the intervention group achieved significantly greater weight loss than the usual care group (-4.8 kg vs -0.6 kg, p &amp;lt; 0.001) regardless of genotype. Conclusions: Common variants of known obesity-associated genes (FTO, MC4R, BDNF, and MC4R) did not modify the effect of the nutrition and exercise intervention on changes in body weight and body fat. Women who are genetically predisposed to obesity and recently diagnosed with breast cancer may benefit from lifestyle changes similarly to women who are not genetically predisposed to obesity. Our findings may help guide the incorporation of lifestyle interventions and weight loss counseling into breast cancer survivorship care. Citation Format: ThaiHien Nguyen, Melinda L Irwin, Andrew T Dewan, Maura Harrigan, Brenda Cartmel, Tara Sanft, Lingeng Lu, Fangyong Li, Yasmmyn D Salinas. Assessing effect modification of obesity-associated genes variants in FTO, MC4R, BDNF, and CREB1 on weight loss among breast cancer survivors enrolled in the randomized lifestyle, exercise, and nutrition (LEAN) study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-17.

In depth analysis of the association of FTO SNP (rs9939609) with the\xa0expression of classical phenotype of PCOS: a Sri Lankan study

BackgroundPCOS is a common disorder of women due to genetic, endocrine and environmental effects that manifests from puberty. The rs9939609 variant of fat mass and obesity associated (FTO) gene is linked to metabolic derangement in PCOS. We previously identified FTO (rs9939609) as a susceptibility locus for PCOS among Sri Lankan women and also explored the role of kisspeptin. Associated factors of the FTO candidate gene among South Asians with PCOS are unknown.MethodsThis study aimed to determine the association between FTO (rs9939609) polymorphism with clinical (BMI, acanthosis nigricans, hirsutism) and biochemical (serum kisspeptin and testosterone levels) characteristics of PCOS in a cohort of Sri Lankan women. Genetic and clinical data including serum kisspeptin and testosterone concentrations of our previously reported cases (n = 55) and controls (n = 110) were re-analyzed, specifically for an association with rs9939609 variant of FTO gene.ResultsLogistic regression analysis (AA – OR = 5.7, 95% CI = 2.41–13.63, p < 0.05) and genetic inheritance analysis (AA – OR = 5.49, 95%CI = 2.34–12.88, p < 0.05) showed that FTO (rs9939609) polymorphism is significantly associated with PCOS and its metabolic manifestations. Serum testosterone was significantly higher in affected women with mutant genotypes (AA+AT) than with the normal allele (TT) (p < 0.05). Although serum kisspeptin was higher in subjects with PCOS and mutant alleles than controls, this difference was not significant (p > 0.05).ConclusionFTO gene variant rs9939609 is associated with hyperandrogenemia and metabolic manifestations of PCOS among women of Sri Lankan descent with the well-characterized phenotype. Serum kisspeptin and the FTO genotypes lack a significant association when adjusted for confounders.

Influence of the A/T polymorphism of the FTO gene and sport specializations on the body composition of young Russian athletes.

Background: The polymorphism in FTO gene (rs9939609) is known to be associated with higher BMI and body fat mass content. However, environmental factors can modify this effect. The purpose of the present study was to investigate an association between sport specialization and the rs9939609 SNP in FTO gene in the cohort of professional and amateur young athletes. Methods: A total number of 250 young individuals 8-18 years old living in Moscow or Moscow district participated in the study. Individuals were divided into 3 groups in accordance with their physical activity level: control group (n = 49), amateurs (n = 67) and professionals (n = 137). Amateur and professional athletes were subdivided into groups according to their sport specialization. Quantile regression was used as a regression model, where the dependent (outcome) variable was BMI, along with percentage of body fat mass, and the independent variables (predictors) were the rs9939609 SNP in FTO gene, physical activity (active versus inactive), sport specialization (aerobic, intermittent sports and martial arts), nationality, level of sport experience (in years), gender and percentage of free fat mass content. Results: The regression analysis revealed that physical activity and sport specialization had greater impact compared to FTO allele in the group of physically active individuals. Physical activity, in particular aerobic, had negative associations with body fat mass and BMI. The rs9939609 SNP in FTO gene is associated with physical activity and aerobic activity. The magnitude of association becomes significantly larger at the upper quantiles of the body fat mass distribution. Conclusion: Physical activity and sport specialization explained more variance in body composition of physically active young individuals compared to the FTO polymorphism. Effect of interaction of physical activity, in particular aerobic, with the FTO polymorphism on body composition of young athletes was found.

Interrelation of the FTO rs9939609 SNP and the DAT1 rs27072 SNP with Body Mass Index and Degree of Obesity in the Population of Yakuts

Interrelation of the FTO rs9939609 SNP and the DAT1 rs27072 SNP with Body Mass Index and Degree of Obesity in the Population of Yakuts

Interaction effects of FTO rs9939609 polymorphism and lifestyle factors on obesity indices in early adolescence

BackgroundThe rs9939609 SNP in fat mass and obesity-associated (FTO) gene influence obesity, whose effects might be mediated by lifestyle factors. However, evidence was lacked in early adolescents. This study aimed to investigate the interactions effects of FTO rs9939609 and lifestyle factors on obesity indices in early adolescence. MethodsThe study included 1149 children aged 10–12 years. Their body mass index (BMI) and body fat percentage (BF%) were measured, and lifestyle factors were surveyed through questionnaires. The rs9939609 SNP in the FTO gene was genotyped. ResultsSignificant associations were found between FTO rs9939609 and obesity indices after adjusting for confounding factors. An interaction effect between rs9939609 and soft drinks was observed with p=0.019 for BMI after adjustment for confounding factors. The children carrying risk allele A had a significantly higher mean BMI (mean=19.67kg/m2) than those carrying only the wild allele T (mean=17.987kg/m2) when they reported a higher intake of soft drinks (≥3 times/week), but the association was not observed among children with a lower intake of soft drinks. No significant interactions were established between appetite, weekday TV viewing, sleep, exclusive breast feeding in the first four months and FTO rs9939609 on BMI or BF%. Bioinformatics revealed that rs9939609 and its linkage disequilibrium (LD) SNPs are potentially implicated in the regulation of gene expression in blood, pancreatic and brain tissue cells. ConclusionFTO rs9939609 had an obvious and independent effect on obesity-related indices in early adolescents. Soft drinks may exert a modifying effect on the relationship between FTO rs9939609 and BMI.

The FTO Gene and Measured Food Intake in 5- to 10-Year-Old Children Without Obesity.

Genetic variation in the first intron of FTO (e.g., single-nucleotide polymorphism [SNP] rs9939609) is strongly associated with adiposity. This effect is thought to be mediated (at least in part) via increasing caloric intake, although the precise molecular genetic mechanisms are not fully understood. Prior pediatric studies of FTO have included youth with overweight and obesity; however, they have not informed whether a genotypic effect on ingestive behavior is present prior to obesity onset. Therefore, this study investigated the association between FTO and caloric intake in children aged 5 to 10 years without obesity (adiposity ≤ 95th percentile). A total of 122 children were genotyped for rs9939609 and ate ad libitum from a laboratory lunch buffet following a standardized breakfast. Linear regressions, adjusting for body mass, were used to examine the association between FTO "dose" (number of copies of SNP rs9939609) and intake variables. There was a significant association between FTO and total intake. Each risk allele predicted an additional 64 calories, accounting for 3% of the variance. There were no associations between FTO and macronutrient preference, energy density, or diet variety. Results were influenced by race. Results corroborate and extend prior work by showing a dose-dependent effect on food intake in children without obesity.

Impact of a FTO gene risk variant on variables of energy metabolism in adults with obesity class 2 and 3

PurposeThe metabolic consequences of carrying a FTO obesity-promoting risk allele have not been fully elucidated and may be confounded by obesity per se. Against this background, we investigated the impact of FTO allele (SNP rs9939609) on fasting and postprandial energy expenditure and fasting substrate expenditure in a study population of uniformly and similarly obese individuals. ProceduresWe studied a similar number of participants with BMI classes 2–3 (median BMI 42.8 kg/m2) who were either homozygote for the non-risk allele TT (n = 33, numbers increased by enrichment), heterozygote (AT) (n = 32), or homozygote for the risk allele AA (n = 35). Major findingsBasal metabolic rate and postprandial energy expenditure did not differ between FTO-groups. However, fasting respiratory quotient (RQ) was increased in those carrying ≥1 risk allele (p = 0.008), whereas postprandial RQ was not. ConclusionIn this study population, the FTO-risk allele associates with fasting reduced fat and increased carbohydrate oxidation.

The role of the genetic variants IRX3 rs3751723 and FTO rs9939609 in the obesity phenotypes of children and adolescents

ObjectiveWe investigated the association of IRX3 SNP rs3751723 with anthropometric characteristics related to adiposity and potential relationships with FTO SNP rs9939609 in a population of Brazilian children and adolescents. MethodsA total of 871 children and adolescents between 7 and 17 years of age were recruited. Adiposity measurements and biochemical parameters were assessed. The variants were genotyped by real-time PCR. Analysis of multiple linear regression, multiple logistic regression, and generalised multifactor dimensionality reduction (GMDR) adjusted for sex, age and ethnicity were applied to test the polymorphisms association with obesity-related phenotypes and the interaction between them. ResultsThe analyses showed that IRX3 was associated with obesity and fat percentage (BF%). An association of FTO rs9939609 with body mass index (BMI) Z-Score and with waist circumference (WC) was detected. The odds ratios (OR) showed that IRX3 rs3751723 was associated with risk of obesity in additive model (p=0.017), recessive model (p=0.016) and with high BF% in all models. FTO rs9939609 was associated with risk of obesity in additive model (p=0.031), recessive (p=0.033) and with altered WC in all models. GMDR-based predictive models for the risk of obesity, altered WC and high BF% adjusted by age, ethnicity and sex suggested no interaction of the two loci. ConclusionsThe genetic variants rs3751723 and rs9939609 have an influence on the characteristics of adiposity; however, the effects of IRX3 and FTO investigated polymorphisms are independent in relation to adiposity parameters.

Influence of FTO rs9939609 SNP and cardiorespiratory fitness on maximal fat oxidation

Influence of FTO rs9939609 SNP and cardiorespiratory fitness on maximal fat oxidation

FTO rs9939609 Does Not Interact with Physical Exercise but Influences Basal Insulin Metabolism in Brazilian Overweight and Obese Adolescents.

Purpose The rs9939609 SNP (T > A) in FTO gene is associated with obesity and type 2 diabetes. The present study aimed at verifying whether this SNP influenced biochemical outcomes of children and adolescents who are overweight/obese submitted to a program of physical exercise and also if there was influence on basal levels of these biochemical variables. Methods The sample was composed by 432 children and adolescents grouped in three ways (obese, overweight, and normal weight); of these, 135 children and adoloescents who are obese and overweight were submitted to a physical exercise program for 12 weeks. All were genotyped by TaqMan SNP genotyping assay. Results The children and adolescents who are overweight/obese and carriers of AA genotype had higher levels of insulin (p=0.03) and HOMA (p=0.007) and lower levels of glucose (p=0.003), but the SNP did not modulate the response to physical exercise. Conclusions In our study, the rs9939609 AA genotype was associated with parameters related to insulin metabolism but did not interact with physical exercise.

FTO genotype and weight status among preadolescents: Assessing the mediating effects of obesogenic appetitive traits

Polymorphisms in the Fat Mass and Obesity Associated (FTO) gene are robustly associated with overweight and obesity among children, although the underlying mechanisms are poorly understood. We tested if appetitive traits partially mediated the association between FTO genotype and increased BMI among a sample of US preadolescents. Data were from 178 unrelated 9–10 year olds who participated in an experimental study between 2013 and 2015. Children's DNA was isolated from buccal swabs, and the rs9939609 SNP in the FTO gene was genotyped. Children's age- and sex-adjusted BMI z-scores were computed using height and weight measured at the laboratory. Parents completed the Child Eating Behavior Questionnaire that includes three validated scales of habitual appetitive traits related to drive and regulation: satiety responsiveness, enjoyment of food and food responsiveness. Structural equation modeling was used to assess if those traits mediated the relationship between FTO and BMI z-score. The sample of children was 48.9% male and 91.0% non-Hispanic white. FTO distribution was in Hardy Weinberg equilibrium, and 16.3% of participants were homozygous for the high-risk allele. Mean BMI z-score was greatest among those with the high-risk genotype (ANOVA P < 0.01). In separate structural equation models adjusted for the child's sex and maternal education, decreased satiety responsiveness and increased food responsiveness each partially mediated the positive association between the high-risk genotype and increased BMI z-score (P-value for each indirect effect <0.05). Continued research is needed to better understand how other known genetic obesity risk factors may impact appetitive traits among children.

Correlation of Resistin Serum Level with Fat Mass and Obesity-Associated Gene (FTO) rs9939609 Polymorphism in Obese Women with Type 2 Diabetes

AimsThe aim of this study was to detect any association of fat mass and obesity-associated (FTO) rs9939609 variant to metabolic and anthropometric parameters and resistin level as adipokines in Iranian obese women with type 2 diabetes mellitus. Material and MethodsTotally, 42 diabetic and 36 non-diabetic women were selected. The PCR amplicons of FTO gene were sequenced and metabolic, anthropometric parameters and resistin level were measured. ResultsSerum resistin concentrations were not different between diabetic and non-diabetic subjects (p>0.05), while resistin level in diabetic group with AA genotype was lower than that with other genotypes in the same group. In rs9939609 SNP adjusted analysis, insulin and HOMA levels were high in AA genotype. While levels of FBS and HbA1c were higher in AA and AT genotypes. In diabetic group, only TG showed significant difference among three genotypes and mean of TG was higher in TA genotype. No significant correlation between resistin and anthropometric and metabolic parameters was found except for DBP in diabetic patients. ConclusionThere was no significant association between rs9939609 and resistin serum level in type 2 obese diabetic women while percentile ranges (25th, 50th and 75th) of resistin concentrations was high in diabetic group.

BAC transgenic zebrafish reveal hypothalamic enhancer activity around obesity associated SNP rs9939609 within the human FTO gene.

SummarySingle Nucleotide Polymorphisms in FTO intron 1 have been associated with obesity risk, leading to the hypothesis that FTO is the obesity‐related gene. However, other studies have shown that the FTO gene is part of the regulatory domain of the neighboring IRX3 gene and that enhancers in FTO intron 1 regulate IRX3. While Irx3 activity was shown to be necessary in the hypothalamus for the metabolic function of Irx3 in mouse, no enhancers with hypothalamic activity have been demonstrated in the risk‐associated region within FTO. In order to identify potential enhancers at the human FTO locus in vivo, we tested regulatory activity in FTO intron 1 using BAC transgenesis in zebrafish. A minimal gata2 promoter‐GFP cassette was inserted 1.3 kb upstream of the obesity associated SNP rs9939609 in a human FTO BAC plasmid. In addition to the previously identified expression domains in notochord and kidney, human FTO BAC:GFP transgenic zebrafish larvae expressed GFP in the ventral posterior tuberculum, the posterior hypothalamus and the anterior brainstem, which are also expression domains of zebrafish irx3a. In contrast, an in‐frame insertion of a GFP cassette at the FTO start codon resulted in weak ubiquitous GFP expression indicating that the promoter of FTO does likely not react to enhancers located in the obesity risk‐associated region. genesis 53:640–651, 2015. © 2015 The Authors. genesis Published by Wiley Periodicals, Inc.