Gene Variant Rs9939609 Research Articles

FTO gene polymorphisms rs9939609 and the risk of obesity among adults in Western and Asian countries: A systematic review and meta-analysis

BackgroundThe FTO gene polymorphisms rs9939609 have been linked to obesity. It’s essential to note that genetic variations exist between different populations. This study aims to assess the correlation between FTO gene polymorphisms rs9939609 and the risk of obesity in adult populations from both Western and Asian countries. MethodsThis research employed meta-analysis, conducting a comprehensive search across articles available in ProQuest, EBSCO, and PubMed from January 2013 to January 2024. Pooled Odds Ratio (POR) with 95 % CI were computed based on the collected data. Review Manager (RevMan) 5.4.1 and Stata 16.0 were employed for data analysis. ResultsIn Western compared to Asian countries, the FTO rs9939609 variant was found to be significantly associated with obesity in various genetic models: dominant (POR = 1.45 vs 1.45), recessive (POR = 1.33 vs 1.51), co-dominant (first model, POR = 1.56 vs 1.70; second model, POR = 1.30 vs 1.37), and allelic (POR = 1.61 vs 1.56) models. Moreover, in Western countries, the FTO rs9939609 variant’s association with obesity was homogeneous in the recessive and first co-dominant genetic models. In Asian countries, the association between FTO rs9939609 and obesity was homogeneous in the dominant, recessive, and co-dominant genetic models (I2<50 %). ConclusionThis study has confirmed that in specific models (such as the recessive and co-dominant models), the correlation between the FTO gene variant rs9939609 and the risk of obesity more significant in Asian countries.

Fat Mass and Obesity-Related (FTO) Gene Variant Is a Predictor of CVD in T2DM Patients.

Background: The role of the common FTO gene variant rs9939609 in obesity has been well established, and the FTO gene has a strong association with T2DM. Objective: To investigate the association of FTO gene variant rs9939609 with obesity-related parameters in T2DM and CVD patients. Materials and Methods: In this cross-sectional study, 280 subjects of either sex aged 45.10 ± 9.6 years were randomly divided into four groups, that is, T2DM, T2DM with CVD, nondiabetic with CVD disease, and normal control. These samples were genotyped by ARMS-PCR. The FTO gene association with obesity-related parameters in T2DM and CVD patients was analyzed by SPSS 22. Results: The TT genotype was the most common genotype (46.80%) in our study groups. The minor allele frequency (MAF) was significantly higher in T2DM patients (0.39 vs. 0.28), T2DM patients with CVD (0.43 vs. 0.28), and nondiabetic patients with CVD (0.35 vs. 0.28) as compared to control with p < 0.005. Carriers of the AA genotype of the FTO gene rs9939609 were significantly associated with increased BMI, WC, HbA1C, SBP, DBP, and TGs and lowered HDL cholesterol as compared to the TA and TT genotypes in T2DM and CVD patients with p < 0.005. The FTO gene variant rs9939609 showed a significant association with T2DM and CVD. The AA genotype odds ratio (OR) in T2DM was 1.48 (1.06-2.32), p = 0.006, and in CVD, it was 1.56 (1.04-2.4), p = 0.003. Conclusion: The FTO gene variant rs9939609 has a strong association with T2DM and CVD. The AA genotype of FTO gene variants rs9939609 showed a strong association with most of the risk factors of CVD and T2DM.

DEVELOPMENT OF PCR-BASED GENOTYPING METHOD FOR FAT MASS OBESITY-ASSOCIATED (FTO) GENE POLYMORPHISM RS9939609

Malaysia has the highest obesity rate in Southeast Asia and is growing. Environmental and genetic factors influence weight increase and obesity, leading to numerous diseases and mortality. This study aimed to develop a genotyping method to detect FTO gene variant rs9939609, known for its association with body mass index (BMI) and obesity. In-house primers detected rs9939609. Two common primers flanked the variation region, and two more primers identified the wild type and alternative allele. Capillary sequencing verified results. We developed FTO gene variant rs9939609 genotyping. This method can be used to genotype FTO variant rs9939609 in any research.

Association of FTO gene variant rs9939609 with polycystic ovary syndrome from Gujarat, India

BackgroundPolycystic ovary syndrome is a multifactorial endocrine disorder impacting women of reproductive age. Variations within the FTO gene have been linked to both obesity and type 2 diabetes mellitus. Given that PCOS is frequently associated with obesity and compromised glucose tolerance, we investigated the prevalence of the rs9939609 variant within the FTO gene among women diagnosed with PCOS and a control group. Our aim is to uncover potential correlations between this genetic variant, metabolic attributes, and endocrine markers within the Gujarat province of India.MethodWe enrolled a total of 114 participants, (62 individuals diagnosed with PCOS and 52 healthy controls). DNA extraction from venous blood was conducted for all participants. The rs9939609 polymorphism was investigated through tetra-primer amplification refractory mutation system-polymerase chain reaction. Furthermore, we performed biochemical assessments to quantify levels of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), total testosterone, prolactin (PRL), and Dehydroepiandrosterone sulfate (DHEAS). Statistical analyses were carried out utilizing SPSS version 21 (IBM, USA).ResultsThe present study did not reveal any noteworthy association between cases and controls. The frequencies of genotypes and alleles within the cohorts displayed no statistically significant differences (p = 0.25, p = 0.68, and p = 0.78, respectively). The dominant model indicated a modest risk (OR:1.13, 95%CI: 0.55 to 2.38) toward PCOS development. There was a noticeable statistical difference observed in the levels of total testosterone, DHEAS, and BMI between the case and control groups (p < 0.002, p < 0.0002, p < 0.0008). However, no variations in clinical variables were observed among genotypes within the PCOS group.ConclusionThis is the first study to investigate the association of FTO gene polymorphism and PCOS in Gujarati population. Our study findings indicate that the FTO gene variant is not directly linked to the onset of PCOS. However, it appears to exert an influence on metabolic factors such as obesity and insulin resistance. Notably, our results suggest that insulin resistance is more frequently observed among PCOS patients who are obese, as compared to those with non-obese PCOS patients.

A single FTO gene variant rs9939609 is associated with weight change and insulin resistance improvement in response to a robotic sleeve gastrectomy in individuals with severe obesity.

Genetic mechanisms have been involved in the weight response secondary to bariatric surgery. The aim of our study was to evaluate the effects of the rs9939609 genetic variant on weight loss and metabolic parameters after sleeve gastrectomy. Tertiary hospital. A total of 95 participants were enrolled. Co-morbidities, biochemical evaluation, and anthropometric parameters were registered before and after 3-, 6-, and 12-month follow-up. Genotype of the rs9939609 fat mass and obesity-associated (FTO) gene was evaluated. We grouped the participants into 2 groups: carriers of A allele (TA+AA, 69.5%) and noncarriers of A allele (TT, 30.5%). We detected a statistically significant reduction of blood pressure, biochemical, and anthropometric parameters at 3 times during follow-up. After 6 months, changes of some parameters were greater in non-A allele carriers: weight (-39.6 + 4.0 kg versus -24.6 + 2.8 kg; P = .02), waist circumference (-21.1 + 2.1 cm versus -16.2 + 1.8 cm; P = .04), insulin (-12.3 + .9 mUI/L versus -8.9.1 + .2 mUI/L; P = .02), and homeostasis model assessment of insulin resistance (-3.1 + .1 units versus -2.3 + .1 units; P = .02 ). After 12 months, changes of the aforementioned parameters remained greater in non-A allele carriers. The percentage of participants with diabetes diminished earlier in the non-A allele carriers than A allele carriers at 6-month follow-up. The percentage of participants with diabetes at the end of the study was lower in non-A allele carriers (3.4% versus 12.1%; P = .02). Our data suggest that non-A allele carriers of the genetic variant (rs9939609) of the FTO gene showed a better improvement of anthropometric and insulin levels in non-A allele carriers after a robotic sleeve gastrectomy. Both improvements are associated with a lower percentage of participants with diabetes at 12 months.

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.

Association of FTO gene variants rs9939609 and rs1421085 with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is among the most common complex genetic endocrinopathy, and its etiology and pathophysiology remain controversial. FTO is a large highly polymorphic gene and was coined as the first locus associated with adiposity. The association of the intronic variant FTO rs9939609 or FTO rs1421085 with PCOS has been controversial and unclear, mainly due to ethnic differences among populations. The present study aims to investigate the association of FTO rs9939609 or FTO rs1421085 polymorphisms with PCOS in Saudi Arabian women.ResultsA total of 98 PCOS patients and 99 healthy females were included in this study. PCR and genotyping (TaqMan®SNP Genotyping Assay) were employed. For FTO rs9939609, the genotype TA and the recessive model (TA + AA) in PCOS patients were significantly different compared with control subjects (p = 0.008 and p = 0.007, respectively). The allele frequency of the FTO rs9939609 gene variant was associated significantly (p = 0.027) with PCOS, suggesting that the A allele is a risk factor for PCOS susceptibility. However, for the FTO rs1421085 variant, the genotype and allele distributions did not differ significantly between PCOS patients and controls (p > 0.05).ConclusionsThis is the first report to study the association of FTO rs9939609 and FTO rs1421085 with PCOS in Saudi women. Results suggest that the FTO rs9939609 gene variant could be a genetic predisposing factor for PCOS Saudi women.

Frequency distribution and association of Fat-mass and obesity (FTO) gene SNP rs-9939609 variant with Diabetes Mellitus Type-II population of Hyderabad, Sindh, Pakistan.

Background/AimDiabetes Mellitus (DM) is one of the important public health issues worldwide. The Fat mass obesity (FTO) gene rs-9939609 variant identified single nucleotide polymorphism (SNP) with the T to A missense mutation, and has a strong association with T2DM. FTO gene is present on chromosome “16q12.2” comprising of nine exons. FTO gene rs-9939609 a variant is commonly found in the Pakistani Population. The purpose of the study was to alert the population about the rs-9939609 variant SNP, having a strong association with T2DM.Material and MethodsTotal of 190 participants were included in the present cross-sectional study. To collect the samples non-probability convenience technique was used. subjects were recruited and divided into three groups, normal healthy subjects, obese and T2DM. The patients were selected from the Medicine department Jamshoro/Hyderabad by filling the pre-designed proforma, as well as verbal and written consent taken from study participants. To analysed the data ANOVA Post hoc (Tukey-test) was applied for comparison among groups (P < 0.05) and “SNP-STAT” online software was used for frequencies.ResultsThe BMI, neck circumference, waist circumference and lipid profile, fasting blood sugar and HbA1c was found significant (p < 0.001) in both genders as compared to control. Homozygous and heterozygous distribution of allelic and genotyping frequency was found in study participants. 37.9 %T/A, 57.4% T/T, and A/A were 4.7%. The FTO gene rs-9939609 variant amplified and have an increased risk of developing T2DM in the Sindh population. Codominant model odd ratio of T/A showed 2.42 (CI)1.23–3.84, with significant p < 0.032.ConclusionThe present study concluded that the FTO gene SNP rs-9939609 variant was found in the population of Hyderabad, Sindh and having strong association with T2DM and obese individuals. Increase BMI, neck and waist circumference are the biomarkers of obesity and causative factors of T2DM.

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.

Gene-diet interaction of FTO-rs9939609 gene variant and hypocaloric diet on glycemic control in overweight and obese adults: a systematic review and meta-analysis of clinical trials.

Background:The hypocaloric diets improve glycemic status in obese individuals, but the response to hypocaloric diets in fat mass and obesity-associated gene (FTO)-rs9939609 gene variant is unknown. This systematic review and meta-analysis aimed to assess the gene-diet interaction of FTO-rs9939609 gene variant and hypocaloric diets on glycemic control in overweight and obese adults.Methods:Cochrane Central Register of Controlled Trials, PubMed, ISI Web of Science, Embase, Scopus, and Google scholar were searched up to December 2018, for relevant clinical trials. Mean changes in fasting blood sugar (FBS), serum insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were extracted.Results:The pooled analysis of nine studies showed that there was no significant difference between AA/AT and TT genotypes in FBS (weighted mean difference [WMD] = 0.01, 95% confidence interval [CI]: –1.08, 1.10, P = 0.984) and serum insulin (WMD = 0.20, 95% CI: –0.85, 1.26; P = 0.707) after intervention hypocaloric diets. The overweight/obese participants in AA/AT group showed the greatest reduction in HOMA-IR compared with TT genotype following intervention, and this difference was not statistically significant (WMD = –0.38, 95% CI: –0.94, 0.16, P = 0.167).Conclusion:This meta-analysis suggests that there was no significant difference between AA/AT and TT genotypes of FTO-rs9939609 on FBS, serum insulin level, and insulin resistance in response to hypocaloric diets.

Ancestry specific associations of FTO gene variant and metabolic syndrome

Cross-sectional studies indicate that the fat mass and obesity-associated (FTO) rs9939609 gene variant is associated with metabolic syndrome (MetS) primarily in European ancestry. However, the association is not fully elucidated in African Americans.We hypothesized that rs9939609 (AT = moderate-risk carriers or AA = high-risk carriers compared to TT = low-risk carriers) is associated with MetS and its component risk factors over time; and that its association is ancestry-specific. A secondary hypothesis was that higher levels of physical activity can decrease the deleterious effect of rs9939609 at higher body mass index (BMI).Atherosclerosis Risk in Communities study repeated measures data from 4 visits (1987–1998) were obtained from the database of Genotypes and Phenotypes for 10,358 participants (8170 Whites and 2188 African Americans) aged 45 to 64 years at baseline. Guidelines for elevated blood pressure by the American College of Cardiology and American Heart Association Task Force were updated within the MetS criteria. Risk ratios (RR) and 95% confidence intervals from generalized estimating equations assessed population-average risks.MetS was present among 3479 (42.6%) Whites and 1098 (50.2%) African Americans at baseline, and 50.3% Whites and 57% African Americans over 11-years of follow-up. Among MetS component risk factors, high waist circumference was most prevalent among White AT (RR = 1.07; 1.06–1.09) and AA (RR = 1.12; 1.10–1.14) higher-risk carriers. High triglycerides were elevated among African American AA high-risk carriers (RR = 1.11; 1.02–1.21) compared to TT low-risk carriers. Over time, White AT-and AA higher-risk carriers had 1.07 and 1.08-fold increase (P < .0001) in MetS risk. Physical activity had independent protective effects on MetS among both races (P < .05). White AA high-risk carriers with normal BMI and low vs high physical activity had higher MetS risk (RR = 1.69; 1.25–2.30 and RR = 0.68;0.53–0.87, respectively). In rs9939609 × BMI× physical activity interaction, White A-allele high-risk carriers had lower MetS risk (RR = 0.68; 0.53–0.87). Among Whites, physical activity can lessen the effect of rs9939609 and high BMI on risk for MetS.

70-LB: Fat Mass and Obesity-Associated rs9939609 Gene Variant Is Related to Fasting Glucose in Children with Mental Health Conditions

Over one million Canadian children are estimated to have a mental health condition, such as depression, anxiety, and attention deficit hyperactivity disorder. Many are treated with second-generation antipsychotics (SGA). In some children, SGA treatment is associated with excessive weight gain and metabolic complications including a 3-fold greater risk for type 2 diabetes. We currently have no way to identify SGA-treated children at risk for metabolic complications. The goal of our study is to determine if the fat mass and obesity-associated gene (FTO) rs9939609 variant is associated with metabolic complications in SGA-treated children. A cross-sectional population of SGA-treated (n=232) and SGA-naïve (n=378) children (≤18y) were recruited through Child and Adolescent Psychiatry at BC Children’s Hospital. Participants were genotyped, metabolic markers assessed; dietary intakes were estimated in a subset of children (n=79). The FTO rs9939609 variant genotype frequencies were not different between SGA-treated (TT 44%, TA 38%, AA 18%) and SGA-naïve (TT 42%, TA 39%, AA 19%) children. An interaction was found between SGA status and FTO genotype for fasting glucose (p=0.014). In SGA-naïve children, the A allele carriers compared to non-carriers had higher fasting glucose (4.95 vs. 4.78 mmol/L; p=0.001) in a model adjusted for age, sex, ethnicity, and zBMI. This difference was not observed in SGA-treated children. Daily energy intakes of A allele carriers were not significantly higher compared to non-carries in SGA-treated (1855 vs. 2087 kcal) and SGA-naïve (1606 vs. 1871 kcal) children. Our findings suggest that the A allele of the FTO rs9939609 variant is associated with higher fasting glucose in SGA-naïve children with mental health conditions. Disclosure A.M. Wiedeman: None. Y. Ngai: None. A.M. Henderson: None. C. Panagiotopoulos: Advisory Panel; Self; Dexcom, Inc. A.M. Devlin: None. Funding BC Mental Health &amp; Substance Use Services

The Influence of FTO Polymorphism rs9939609 on Obesity, Some Clinical Features, and Disturbance of Carbohydrate Metabolism in Patients with Psoriasis.

Background Psoriasis is often accompanied by obesity, hyperlipidemia, diabetes, and metabolic syndrome as risk factors of cardiovascular conditions and premature mortality. Objective The study was aimed at investigating whether psoriatic patients, who carry risk allele of obesity-related FTO gene, are more predisposed to obesity and metabolic disturbances and whether it influences the severity of psoriasis. Methods 197 patients with psoriasis, representing Lower Silesia region of Poland, underwent physical examination and anthropometric measurements. Blood samples for biochemical and genetic analysis were collected. All patients were genotyped for FTO gene rs9939609 variant. Identification of SNP was conducted with the use of minisequencing method. Results Around 63% of patients were carriers of at least one risk allele A and 20% were AA homozygotes. The A allele was associated with increased BMI and hip and waist circumferences. The carriers of risk allele had increased PASI and CRP values and tended to have an increased insulin concentration. Conclusion Psoriatic patients, carriers of risk allele of FTO gene rs9939609, have an increased risk for more severe psoriasis and obesity and may develop obesity-induced insulin resistance.

Fat Mass and Obesity-Related Gene Variants rs9939609 and rs7185735 are Associated with Second-Generation Antipsychotic-Induced Weight Gain

Weight gain is a limiting and frequent adverse effect of second-generation antipsychotic therapy. Identifying genetic risk factors would significantly improve pharmacotherapy. We focused on rs7185735 and rs9939609, 2 common single nucleotide polymorphisms of the fat mass and obesity-associated (FTO) gene reported to be associated with obesity. Three-hundred fifty Caucasian inpatients were included in a naturalistic study. After 4 weeks of treatment, we did not observe any significant association of polymorphisms with weight change in the whole study population (p>0.05). In a subpopulation without additional weight-inducing comedication (n=178), G-allele carriers of rs7185735 gained 3.4 times more weight (1.69 kg±3.1 kg, p=0.019) than AA genotypes (0.49 kg±3.1 kg). A-allele carriers of rs9939609 gained 3.1 times more weight (1.65 kg±3.1 kg, p=0.029) than TT genotypes (0.54 kg±3.2 kg). Our findings confirm the role of the FTO gene as a high-potential risk factor for obesity and indicate a value for predicting a weight gain induced by second-generation antipsychotics. Further, we detected an additive effect of FTO rs7185735 and MC4R rs17782313.

Adolescent obesity and the role of the fat mass and obesity-associated gene polymorphism.

The association between fat mass and obesity-associated (FTO) gene and obesity is unclear in both adults and adolescents. The aim of this study was to examine the role of the FTO gene variant rs9939609 as a candidate gene for obesity and the relationship between insulin resistance (IR), metabolic syndrome (MetS), estimated glomerular filtration rate (eGFR) and neutrophil-to-lymphocyte ratio (NLR). Obese adolescents (n=100) and healthy controls (n=100) were included. Rs9939609 polymorphism in the FTO gene was genotyped by PCR-SNaPshot. The prevalence of insulin resistance (IR), metabolic syndrome (MetS) and hyperfiltration were 47%, 60% and 27%, respectively. There were no significant differences in genotype and allele frequencies between obese adolescents and controls; however, prevalence of MetS in female patients with A allele carriers was more frequent and prevalence of hyperfiltration was less frequent with T allele carriers (P.

Association of Fat Mass and Obesity-associated Gene (FTO) rs9939609 Variant with Early Onset Obesity among Bataknese and Chinese Children in Indonesia: A Case-control Study

BACKGROUND: Childhood obesity is associated with the risk of adult obesity and obesity-related chronic disease. The fat mass and obesity-associated gene (FTO) rs9939609 variant are of particular interest because of its association with body mass index (BMI) and obesity-related phenotypes. This study was conducted to investigate the association between FTO gene rs9939609 variant with early onset obesity among Bataknese and Chinese children in Medan, Sumatera Utara, Indonesia.METHODS: The case-control study was carried out at 10 elementary schools in Medan. There were 212 children recruited; 56 early onset obesity and 61 control Bataknese and 49 early onset obesity and 46 control Chinese children. This study included a questionnaire, anthropometric measurements, and blood test analysis. rs9939609 polymorphism genotyping was performed using RT-PCR. Logistic regression, odds ratio (OR) and 95% confidence interval (CI) were calculated to determine the risk of obesity associated with the risk alleles, p&lt;0.05 was considered as statistically significant.RESULTS: This study found a significant association between rs9939609 and early onset obesity in Chinese children (p=0.01), but not in Bataknese. The frequency of AA genotype was lower in the early onset obesity than in the normal weight children, while an OR of 0.69 showed that this genotype may protect against weight gaining and that the TT genotype may predispose to obesity.CONCLUSION: We concluded that the FTO gene rs9939609 is associated with early onset obesity in Chinese ethnicity but not in Bataknese.KEYWORDS: pediatric obesity, FTO gene, rs9939609, polymorphism, Indonesia

FTO gene polymorphisms (rs9939609 and rs17817449) as predictors of Type 2 Diabetes Mellitus in obese Iraqi population

BackgroundThe variation of the SNPs in FTO (fat mass and obesity associated) gene are improved to be associated with obesity and type 2 diabetes (T2DM) in some ethnic groups for example in European while, this consistency is controversial in Asians and there were few studies in Iraqi population about the effect of this gene on the development of T2DM in obese patients. Therefore, the objective of this study is to investigate the impact of the two common FTO gene variants in the development of T2DM in obese Iraqi patients. MethodsA case-control study in which the FTO gene variants rs9939609 and rs17817449 were genotyping in a total of 800 individuals, 400 T2DM obese patients (patients group) and 400 healthy control obese volunteers (control group) to explore the relation of these SNPs with T2DM in obese Iraqi population. The patients group was enrolled from diabetic clinic in Al Najaf al Ashraf based on WHO guidelines of T2DM. From whole blood the DNA was extraction and genotyped by using ScaI and AlwNI enzymes respectively in the PCR–RFLP technique. Multinomial logistic regression was applied to compare the proportions of genotypes and alleles. The odd's ratio, t-test P value at 95% confidence interval were measured before and after adjustment of BMI, age and sex adjustment. The genetic power, Hardy Weinberg equilibrium and haplotype analysis were tested in the present study. ResultsIt was observed that the presence of T allele in the two SNPs rs9939609 and rs17817449 in the FTO gene polymorphisms was associated with increased risk for the development of T2DM in Iraqi obese individuals. The minor allele (T) in rs9939609 was significantly higher (P=0.0001) in T2DM (31.25%) when compared with that of the control obese group (20%). The Homozygous genotype (TT) significantly (OR=3.25, CI 95% 1.87–5.64, P=0.000) increased the risk of T2DM by three folds with respect to those of wild type (AA) after adjustment for age, sex and BMI, furthermore, it was significantly increased the risk in the dominant, recessive and additive models (P=0.000,0.000 and 0.0001 respectively). The T allele in rs17817449 was also significantly higher (P=0.0001) in patients group (36.25%) when compared with that of the control group (27.25%). The Heterozygous genotype (TG) significantly (OR=2.24, CI 95% 1.65–3.04, P=0.000) increased the risk of T2DM more than two folds with respect to those of wild type (GG) after adjustment for age, sex and BMI, and it was significantly increased the risk in the dominant models (P=0.000). In the relation to the phenotypic parameters the two SNPs were significantly associated with increased BMI, LDL, insulin and HOMA-IR and a decrease the HDL levels. ConclusionThe FTO gene polymorphisms rs9939609 and rs17817449 play a role in the in the development of insulin resistance and hence occurrence of type 2 DM in obese patients.

Association of the rs9939609 gene variant in FTO with insulin resistance, cardiovascular risk factor and serum adipokine levels in obese patients.

The aim of our study was to analyze the relationship of the rs9939609 FTO gene polymorphism with insulin resistance and serum adipokine levels. A population of 610 patients with obesity was analyzed in a cross sectional design. Weight, blood pressure, basal glucose, c-reactive protein (CRP), insulin, insulin resistance (HOMA), lipid profile and adipocytokines (leptin, adiponectin, resistin, TNF alpha, and interleukin 6) levels were measured. Insulin (122.2 ± 101.8 pmol/L vs. 104.5 ± 61.5 pmol/L vs.112.1 ± 74.3 pmol/L:p < 0.05) and HOMA-IR values (4.76 ± 4.4 vs. 3.71 ± 2.5 vs.3.76 ± 3.1;p < 0.05) were higher in TT group than AT and AA groups. Triglycerides values were higher in TT group than AA group (1.42 ± 0.71 mmol/L vs.1.39 ± 0.69 mmol/L vs.1.23 ± 0.64 mmol/L;p < 0.05). Adiponectin levels were lower in TT genotype group than AA genotype group (35801.2 ± 35,912.3 ng/L vs.26,718.1 ± 36,323.1 ng/L vs. 21,112.3 ± 25,623.1 ng/L p < 0.05). The FTO gene polymorphism, rs9939609, was found to be associated with insulin resistance, insulin, triglyceride and adiponectin levels in obese patients with TT variant.

FTO rs 9939609 SNP Is Associated With Adiponectin and Leptin Levels and the Risk of Obesity in a Cohort of Romanian Children Population.

Obesity is a disorder with increasing frequency in children and adolescents, directly linked with various diseases. Variants in the FTO (fat mass and obesity-related) gene have been associated with body mass index and waist and hip circumferences in widespread populations.The aim of this case-control study was to assess if there is any association between FTO gene variants rs9939609, respectively, rs17817449 with anthropometric and metabolic biomarkers (fasting glucose, TC, HDL-cholesterol, LDL-cholesterol, triglycerides) and adipokines (adiponectin and leptin), in Romanian obese children.A total of 387 children, 201 obese and 186 nonobese individuals, were included in this prospective study. Genotyping of the FTO gene polymorphisms for all subjects was performed using the restriction fragment length polymorphism (PCR–RFLP) method.Significant associations were found between FTO rs9939609 single nucleotide polymorphism (SNP) and obesity. AA genotype carriers have a 2.02 times higher risk for obesity compared with AT+TT genotype carriers. Risk allele carriers of rs17817449 SNP had somewhat higher values of weight, body mass index, waist and hip circumference, total cholesterol, triglycerides, adiponectin, and fasting glucose.This study revealed the genetic association between rs9939609 SNP of FTO and obesity in a Romanian population, and to the authors’ knowledge, this is the first study to investigate this association in a Romanian population. This study also established that combined variant genotypes (AA/GG) of FTO rs9939609 /rs17817449 are strongly associated with several measures of adiposity (weight, BMI-SD, mid-upper arm circumference, tricipital skinfold thicknesses) and are also associated with total cholesterol, triglyceride, and LDL-cholesterol levels.

Physical activity, but not dietary intake, attenuates the effect of the FTO rs9939609 polymorphism on obesity and metabolic syndrome in Lithuanian adult population

ObjectivesThis study aimed to examine the associations between the fat mass and obesity associated (FTO) gene rs9939609 variant with obesity and metabolic syndrome and interactions between FTO alleles, dietary intake and physical activity in Lithuanian adult population. Study designCross-sectional study. MethodsA health survey was carried out in randomly selected municipalities of Lithuania. The random sample was obtained from the lists of 25–64 year-old inhabitants. The data from 1020 individuals were analyzed. The single-nucleotide polymorphism, rs9939609, in the FTO gene was assessed using a real-time polymerase chain reaction. 24-hour recall was used for evaluation of dietary habits. Information on physical activity at work, traveling to and from work and at leisure time was gathered by a standard questionnaire. ResultsThe carriers of the AA genotype had the highest mean values of body mass index (BMI) and waist circumference (WC). They had 1.72 time higher odds of obesity (P = 0.009) and 1.67 time higher odds of increased WC (P = 0.013) than those with the TT genotype. Carriers of the T allele had lower prevalence of metabolic syndrome compared to carriers of the AA genotype (33.8% and 42.5% respectively; P = 0.018). No interaction between the rs9939609 variant and energy or dietary intakes on weight status was found. Significant effect of the interactions ‘genotype×age’ and ‘genotype×physical activity’ on BMI was demonstrated. The FTO rs9939609 polymorphism was associated with anthropometric parameters and metabolic syndrome in the younger age group (25–44 years) and in individuals having low level of physical activity. ConclusionsAge and physical activity modulated the effect of the FTO polymorphism on weight status and metabolic syndrome in Lithuanian adult population.