The FTO rs9939609 and LEPR rs1137101 mothers-newborns gene polymorphisms and maternal fat mass index effects on anthropometric characteristics in newborns: A cross-sectional study on mothers-newborns gene polymorphisms-The FTO-LEPR Study (STROBE-compliant article).
ABSTRACT: The aim of this study was to assess the impact of mothers' and newborns' fat mass and obesity-associated gene (FTO) rs9939609 and leptin receptor (LEPR) rs1137101 gene polymorphisms on neonatal anthropometric parameters in order to identify a potential risk for developing obesity.We performed a cross-sectional study on 355 mother-newborn couples in an Obstetrics Gynecology Tertiary Hospital from Romania, evaluated with regard to anthropometric parameters, clinical and laboratory parameters besides 2 genetic polymorphisms (FTO rs9939609 and LEPR rs1137101).Newborns with mothers carrying variant AT or AA genotype for FTO rs9939609 presented lower BMI (P = 0.012) and lower MUAC (P = 0.029). There was a significant interaction effect between newborn and mother LEPR rs1137101 polymorphism on birth weight (P = 0.009) and BMI (P = 0.007). We noticed significantly increased birth weight and BMI in newborns carriers of AG?+?GG genotype, coming from mothers with AA genotype (P = 0.006). There was no evidence of significant interaction effect between newborn and mother FTO rs9939609 polymorphism on the studied anthropometrical data (P?>?0.05). In addition, lower BMI scores (P = 0.042) were observed in newborns carriers of TT genotype whose mothers had AA?+?AT genotype. Lower MUAC scores (P = 0.041) were noticed in newborns carriers of AA?+?AT genotype whose mothers had AA?+?AT genotype for FTO rs9939609 gene polymorphism. Newborns carriers of the AG?+?GG genotype (P = 0.003) of LEPR rs1137101 coming from mothers with increased FMI (upper tertile) had significantly increased BMIs.Presence of the variant A allele of FTO rs9939609 polymorphism in mothers decreased BMI and MUAC in newborns. The impact of LEPR rs1137101 polymorphism on BMI and birth weight in newborns differed depending on the presence/absence of the dominant LEPR allele in mothers. In addition, we noticed that maternal FMI presented a significant positive effect on newborns' BMI by changing the effect of LEPR rs1137101.We can conclude that mothers' FTO rs9939609 and LEPR rs1137101 gene polymorphisms presented an impact on birth weight and newborns' BMI, therefore being involved in the newborns' nutritional status and in the design of a potential protocol.
Project description:PURPOSE:Evaluate the relationship of leptin receptor (LEPR) rs1137101, fat mass obesity-associated (FTO) receptors 9939609, melanocortin-4 receptors (MC4R) rs2229616 and rs17782313, and proliferator-activated receptor-gamma (PPARG) rs1801282 with clinical and metabolic phenotypes in prepubertal children. RESEARCH QUESTION:What is the effect of polymorphisms on clinical and metabolic phenotypes in prepubertal children? METHODS:A cross-sectional descriptive study was performed to evaluate anthropometric features, percentage body fat (%BF), biochemical parameters, and genotype in 773 prepubertal children. RESULTS:FTO rs9939609 was associated with an increase in body mass index (BMI) and BMI z-score (zBMI). MC4R rs17782313 was associated with a decrease in BMI and +0.06 units in zBMI. LEPR, and PPARG-2 polymorphisms were associated with decreases in BMI and an increase and decrease units in zBMI, respectively. The homozygous SNPs demonstrated increases (FTO rs993609 and MC4R rs17782313) and decreases (LEPR rs1137101, PPARG rs1801282) in zBMI than the homozygous form of the major allele. In the overweight/obese group, the MC4R rs17782313 CC genotype showed higher average weight, zBMI, waist circumference, waist-circumference-to-height ratio, and waist-hip ratio, and lower BMI, mid-upper arm circumference, calf circumference, and %BF (P< 0.05). FTO rs9939609 AT and AA genotypes were associated with lower triglycerides (P < 0.05). CONCLUSIONS:We showed that MC4R rs17782313 and FTO rs9939609 were positively associated with zBMI, with weak and very weak effects, respectively, suggesting a very scarce contribution to childhood obesity. LEPR rs1137101 and PPARG-2 rs1801282 had weak and medium negative effects on zBMI, respectively, and may slightly protect against childhood obesity.
Project description:<h4>Purpose</h4>Poor physical fitness and obesity are risk factors for all cause morbidity and mortality. We aimed to clarify whether common genetic variants of key energy intake determinants in leptin (LEP), leptin receptor (LEPR), and fat mass and obesity-associated (FTO) are associated with aerobic and neuromuscular performance, and whether aerobic fitness can alter the effect of these genotypes on body composition.<h4>Methods</h4>846 healthy Finnish males of Caucasian origin were genotyped for FTO (rs8050136), LEP (rs7799039) and LEPR (rs8179183 and rs1137101) single nucleotide polymorphisms (SNPs), and studied for associations with maximal oxygen consumption, body fat percent, serum leptin levels, waist circumference and maximal force of leg extensor muscles.<h4>Results</h4>Genotype AA of the FTO SNP rs8050136 associated with higher BMI and greater waist circumference compared to the genotype CC. In general linear model, no significant interaction for FTO genotype-relative VO(2)max (mL·kg(-1)·min(-1)) or FTO genotype-absolute VO(2)max (L·min(-1)) on BMI or waist circumference was found. Main effects of aerobic performance on body composition traits were significant (p<0.001). Logistic regression modelling found no significant interaction between aerobic fitness and FTO genotype. LEP SNP rs7799039, LEPR SNPs rs8179183 and rs1137101 did not associate with any of the measured variables, and no significant interactions of LEP or LEPR genotype with aerobic fitness were observed. In addition, none of the studied SNPs associated with aerobic or neuromuscular performance.<h4>Conclusions</h4>Aerobic fitness may not modify the effect of FTO variation on body composition traits. However, relative aerobic capacity associates with lower BMI and waist circumference regardless of the FTO genotype. FTO, LEP and LEPR genotypes unlikely associate with physical performance.
Project description:BACKGROUND:The risk of obesity is determined by complex interactions between genetic and environmental factors. Little research to date has investigated the interaction between gene and food intake. The aim of the current study is to explore the potential effect of fat mass and obesity-associated protein gene (FTO) rs9939609 and rs9930506 single nucleotide polymorphism (SNP) on the pattern of food intake in the Emirati population. METHODS:Adult healthy Emirati subjects with Body mass index (BMI) of 16-40 kg/m2 were included in the study. Genotyping for FTO rs9939609(A>T) and rs9930506(A>G) was performed using DNA from saliva samples. Subjects were categorized according to the WHO classification by calculating the BMI to compare different classes. Dietary intake was assessed by a sixty-one-item FFQ that estimated food and beverage intakes over the past year. The daily energy, macronutrient, and micronutrient consumption were computed. RESULTS:We included 169 subjects in the final analysis (mean age 30.49± 9.1years, 57.4% females). The mean BMI of the study population was 26.19 kg/m2. Both SNPs were in Hardy Weinberg Equilibrium. The rs9939609 AA genotype was significantly associated with higher BMI (p = 0.004); the effect was significant in females (p = 0.028), but not in males (p = 0.184). Carbohydrate intake was significantly higher in AA subjects with a trend of lower fat intake compared to other genotypes. The odds ratio for the AA was 3.78 in the fourth quartile and 2.67 for the A/T in the second quartile of total carbohydrate intake, considering the first quartile as a reference (95% CI = 1.017-14.1 and 1.03-6.88, respectively). Fat intake was significantly lower in the FTO rs9930506 GG subjects. The presence of FTO rs9930506 GG genotype decreased the fat intake in subjects with FTO rs9939609 AA (p = 0.037). CONCLUSIONS:The results of this study highlight the interaction of the FTO risk alleles on the food intake in Emirati subjects. The FTO rs9939609 AA subjects had higher carbohydrate and lower fat intake. The latter was accentuated in presence of rs9930506 GG genotype.
Project description:BACKGROUND:Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the fourth leading cause of cancer-related mortality around the world. OBJECTIVES:With regard to the role of obesity in colorectal cancer (CRC) and the role of leptin in obesity, we investigated whether leptin (LEP) and leptin receptor (LEPR) gene variants are associated with CRC risk. PATIENTS AND METHODS:We evaluated LEP (rs7799039) and LEPR (rs1137101) gene variants by using PCR-RFLP method in 261 cases with CRC and 339 controls. RESULTS:No significant difference was found for rs7799039 and rs1137101gene variants between the cases with CRC and controls. However, the LEPR rs1137101 "GG" genotype compared with "AA" genotype and "AA + AG" genotype was associated with increased risks for obesity, and the differences remained significant after adjustment for confounding factors including age, sex, smoking status, and NSAID use (P = 0.015; OR = 2.42, 95%CI = 1.19 - 4.93 and P = 0.016; OR = 2.28, 95%CI = 1.17 - 4.48, respectively). In addition, the LEPR "G" allele compared with the "A" allele was associated with an increased risk for obesity (P = 0.024; OR = 1.44, 95%CI = 1.05 - 1.98). CONCLUSIONS:Consistent with most previous studies, our findings found no association between LEP (rs7799039) and LEPR (rs1137101) gene variants and CRC risk. However, the LEPR rs1137101 "GG" genotype compared with the "AA" genotype and "AA+AG" genotype was associated with a 2.42-fold and a 2.28-fold increased risk for obesity, respectively.
Project description:BACKGROUND:Variations 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. METHODS:The 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. RESULTS:The 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). CONCLUSION:Our 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.
Project description:The Fat Mass and Obesity-Associated Protein (FTO) gene rs9939609 single nucleotide polymorphism (SNP) has been associated with obesity, metabolic syndrome, insulin resistance (IR), and type 2 diabetes mellitus in the general population. The aim of our study was to examine for the first time the association of the rs9939609 polymorphism with metabolic disturbances, liver disease and virologic response to hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin (pegIFN?/RBV) in human immunodeficiency virus (HIV)/HCV coinfected patients.We carried out a cross-sectional study in 261 patients, of whom 178 were subsequently treated with pegIFN?/RBV therapy. FTO rs9939609 and IFNL3 rs12980275 polymorphisms were genotyped by GoldenGate®. The main outcomes were: 1) metabolic disturbances: insulin resistance (homeostatic model assessment (HOMA-IR)) and overweight (body mass index (BMI)); 2) liver disease (Metavir score): significant fibrosis (F ?2) and steatosis (>10% fatty hepatocytes); and 3) virologic response to HCV treatment: sustained virologic response (SVR).The rs9939609 AA genotype was associated with higher values of BMI (adjusted arithmetic mean ratio (aAMR) = 1.08; 95% confidence interval (95%CI) = 1.03 to 1.14; P = 0.002) and HOMA-IR (aAMR = 1.32; 95%CI = 1.03 to 1.69; P = 0.027). Patients with an rs9939609 AA genotype had higher likelihoods of achieving values of BMI ?27.5 kg/m2 (adjusted odds ratio (aOR) = 3.46; 95%CI =1.17 to 10.21; P = 0.024), HOMA-IR ?2.5 (aOR = 2.09; 95%CI = 1.02 to 4.32; P = 0.045), significant fibrosis (aOR = 2.34; 95%CI =1.02 to 5.36; P = 0.045) and steatosis (aOR = 3.65; 95%CI = 1.29 to 10.36; P = 0.015). The rs9939609 AT/AA genotype decreased the likelihood of achieving SVR (aOR = 0.58; 95%CI = 0.34 to 0.99; P = 0.044). A decision tree was performed with the genotypes of HCV, IFNL3 and FTO. The incorporation of rs9939609 significantly improves the prediction of SVR (P <0.05). The overall accuracy was 68.2%.Patients carrying the unfavourable AT/AA genotype of rs9939609 polymorphism had higher odds of metabolic disturbances and a lower likelihood of achieving successful virologic response to HCV therapy.
Project description:BACKGROUND The 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 AND METHODS The 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. RESULTS Body 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. CONCLUSIONS The AT/AA genotype and allele A of rs9939609 are associated with an increased risk of obesity.
Project description:OBJECTIVE:Fat-mass and obesity-associated (FTO) gene is known to be involved in the pathophysiology of obesity and a single-nucleotide polymorphism (SNP) rs9939609 of FTO gene is repeatedly confirmed to be associated with body mass index (BMI) and obesity. The aim of this study is to elucidate effects of FTO gene polymorphism on BMI in Japanese patients with schizophrenia and healthy subjects. METHODS:Three hundred fifty one patients with schizophrenia and 342 age- and sex-matched healthy subjects participated in the study. Information on BMI and antipsychotic medication was also collected from patients and healthy subjects. Genotype of the FTO SNP rs9939609 was determined by TaqMan SNP Genotyping Assays. RESULTS:There was no significant difference in BMI between patients and healthy subjects. No significant difference in BMI was observed among any medications. We observed no significant difference in rs9939609 allele frequencies between patients and healthy subjects. There was a significant difference in BMI between healthy subjects with risk (AA or TA) genotypes and those with TT genotype. We also observed a significant positive correlation between the number of risk allele (A allele) and BMI in healthy subjects. CONCLUSION:Our study suggested that FTO rs9939609 polymorphism might have some impacts on the BMI in healthy subjects, but might not have same impacts on the BMI of patients with schizophrenia.
Project description:Common FTO (fat mass and obesity associated) gene variants have recently been strongly associated with body mass index and obesity in several large studies. Here we set out to examine the association of the FTO variant rs9939609 with BMI in a 32 year follow up study of men born 1920-1924. Moreover, we analyzed the effect of physical activity on the different genotypes.The FTO rs9936609 was genotyped using an Illumina golden gate assay. BMI was calculated using standard methods and body fat was estimated by measuring skinfold thickness using a Harpenden caliper. Physical activity was assessed using a four question medical questionnaire.FTO rs9939609 was genotyped in 1153 elderly Swedish men taking part of a population-based cohort study, the ULSAM cohort. The risk of obesity and differences in BMI according to genotype at the ages of 50, 60, 70, 77 and 82 were investigated. We found no increased risk of obesity and no association with BMI at any age with the FTO rs9939609 variant. We found however interaction between physical activity at the age of 50 years and genotype on BMI levels (p = 0.039) and there was a clear trend towards larger BMI differences between the TT and AA carriers as well as between AT and AA carriers in the less physically active subjects.Here we found that the well established obesity risk allele for a common variant in FTO does not associate with increased BMI levels in a Swedish population of adult men which reached adulthood before the appearance of today's obesogenic enviroment. There is an interaction between physical activity and the effect of the FTO genotype on BMI levels suggesting that lack of physical activity is a requirement for an association of FTO gene variants to obesity.
Project description:Previous studies have suggested that fat mass-and obesity-associated (FTO) gene is associated with body mass index (BMI) and the risk of obesity. This study aims to assess the association of five FTO polymorphisms (rs9939609, rs8050136, rs1558902, rs3751812 and rs6499640) with obesity and relative parameters in Han Chinese adolescents.We examined a total of 401 adolescents, 223 normal weights (58.7% boys, 41.3% girls), 178 overweight (60.1% boys, 39.9% girls), aging from 14 to 18-years-old, recruited randomly from public schools in the central region of Wuxi, a southern city of China. DNA samples were genotyped for the five polymorphisms by Sequenom Plex MassARRAY. Association of the FTO polymorphisms with BMI, serum fasting plasm glucose (FPG), fasting insulin (FIns), triglyceride (TG) and cholesterol (TC) were investigated.1) Serum FPG, FIns, TG and TC were statistically significant higher than that in normal control group. 2) We found that BMI was higher in the rs9939609 TA+AA, rs8050136 AC+AA, rs1558902 TA+AA and rs3751812 GT+TT genotypes than in wild TT genotypes (rs9939609: P = 0.038; rs1558902: P = 0.038;), CC genotypes(rs8050136: P = 0.024) and GG genotypes (rs3751812: P = 0.024), which were not significant on adjusting for multiple testing. 3) In case-control studies, five polymorphisms were not significantly associated with overweight (p>0.05), haplotype analyses showed non-haplotype is significantly associated with a higher risk of being overweight (p>0.05). 4) There existed no significant statistical difference about FPG, FIns, TG and TC in genotype model for any SNP.Our study has conducted a genetic association study of the FTO polymorphisms with BMI, serum fasting plasm glucose (FPG), fasting insulin (FIns), triglyceride (TG) and cholesterol (TC). Our study found BMI of subjects with A allele of FTO rs9939609 is higher than that with T allele. Further studies on other polymorphisms from FTO and increasing the sample size are needed.