The Effects of Genetic Variation in FTO rs9939609 on Obesity and Dietary Preferences in Chinese Han Children and Adolescents

The association of the rs9939609 single nucleotide polymorphism in FTO gene with obesity has been extensively investigated in studies of populations of European, African, and Asian ancestry. However, inconsistent results have been reported in Asian populations, and the relationship of FTO variation and dietary behaviors has only rarely been examined in Chinese children and adolescents. The aim of this study was to assess the association of rs9939609 with obesity and dietary preferences in childhood in a Chinese population. Epidemiological data including dietary preferences were collected in interviews using survey questionnaires, and rs9939609 genotype was determined by real-time PCR. The associations of rs9939609 genotypes with obesity and dietary preferences were analyzed by multivariate logistic regression using both additive and dominant models. The results showed that subjects with a TA or AA genotype had an increased risk of obesity compared with the TT participants; the odds ratios (ORs) were 1.47 (95% CI: 1.25–1.71, P = 1.73×10⁻⁶), and 3.32 (95% CI: 2.01–5.47, P = 2.68×10⁻⁶), respectively. After adjusting for age and gender, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower in TA and AA participants than in those with the TT genotype. After additionally controlling for body mass index, the association remained significant only for systolic blood pressure (P = 0.005). Compared with TT participants, those with the AA genotype were more likely to prefer a meat-based diet (OR = 2.81, 95% CI: 1.52–5.21). The combined OR for obesity in participants with TA/AA genotypes and preference for a meat-based diet was 4.04 (95% CI: 2.8–5.81) compared with the TT participants who preferred a plant-based diet. These findings indicate the genetic variation of rs9939609 is associated with obesity and dietary preferences in Chinese children and adolescents.     

Association of a common rs9939609 variant in the fat mass and obesity-associated (<Emphasis Type="Italic">FTO</Emphasis>) gene with obesity and metabolic phenotypes in a Taiwanese population: a replication study

It is a key challenge to conduct reproducibility in genetic research, especially association studies in obesity. While susceptibility of a single-nucleotide polymorphism (SNP), rs9939609, in the fat mass and obesity-associated (FTO) gene to obesity has been reported in various populations, data from Asians is less conclusive. This replication study was carried out to test whether the FTO rs9939609 SNP is a predictive factor for obesity and obesity-related metabolic traits in a Taiwanese population. A total of 1188 Taiwanese subjects were recruited for this study. The FTO rs9939609 SNP was genotyped by the Taqman assay. Obesity-related metabolic traits such as triglyceride, waist circumference, systolic and diastolic blood pressure, total cholesterol, creatinine, alanine aminotransferase and fasting glucose were measured. Our data revealed that the FTOrs9939609 SNP exhibited a significant association with obesity (BMI \(\geqq \) 30 kg/m ²) among the subjects (P= 0.026). However, the FTO rs9939609 SNP did not exhibit any significant association with obesity-related metabolic traits among the subjects. Our results indicated that the FTO rs9939609 SNP may be linked with the risk of obesity in Taiwanese subjects.     

Interaction between obesity-related genes, FTO and MC4R, associated to an increase of breast cancer risk

Breast cancer (BC) is a complex disease and obesity is a well-known risk factor for its development, especially after menopause. Several studies have shown Single Nucleotide Polymorphisms (SNPs) linked to overweight and obesity, such as: rs1121980 (T/C) and rs9939609 (A/T) in Fat Mass and Obesity Associated gene (FTO) and rs17782313 (T/C) in Melanocortin 4 Receptor gene (MC4R). Thus, we aimed to investigate the association between these obesity-related SNPs and BC risk. One hundred BC patients and 148 healthy women from Santa Catarina, Brazil entered the study. SNPs were genotyped using Taqman assays. For statistical analyses SNPStats and SPSS softwares were used. Association analyses were performed by logistic regression and were adjusted for age and Body mass index (BMI). Multiple SNPs inheritance models (log-additive, dominant, recessive, codominant) were performed to determine odds ratios (ORs), assuming 95 % confidence interval (CI) and P value = 0.05 as the significance limit. When analyzed alone, FTO rs1121980 and rs9939609 did not show significant associations with BC development, however MC4R rs17782313 showed increased risk for BC even after adjustments (P-value = 0.032). Interestingly, the interaction of FTO and MC4R polymorphisms showed a powerful association with BC. We observed a 4.59-fold increased risk for woman who have the allele combination C/T/C (FTO rs1121980/FTO rs9939609/MC4R rs17782313) (P-value = 0.0011, adjusted for age and BMI). We found important and unpublished associations between these obesity-related genes and BC risk. These associations seem to be independent of their effect on BMI, indicating a direct role of the interaction between FTO and MC4R polymorphisms in BC development.     

Association of obesity with rs1421085 and rs9939609 polymorphisms of FTO gene

The aim of this study is to investigate the genetic influence of polymorphisms in fat mass and obesity associated (FTO) gene on a sample of obese subjects and controls. Obesity is an epidemic all over the world. Several polymorphisms in the first intron of FTO gene have been associated with common forms of human obesity. In this research rs1421085 and rs9939609 polymorphisms of FTO gene were genotyped in 190 obese patients with a BMI ≥30 kg/m² (Body Mass Index) and 97 healthy controls with a BMI of 18.5–24.9. Genotyping of SNPs was performed by real-time polymerase chain reaction. Body composition was established with bioelectric impedance analysis. Waist-to-hip ratio was determined for all participants. There were no significant differences (P > 0.05) between obese cases and controls in terms of genotype frequencies of rs1421085 and rs9939609 polymorphisms in our study. Also there were no significant correlations between genotypes and obesity related (anthropometric-body composition) parameters (P > 0.05).     

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project

Genetic factors may interact with lifestyle factors to modify obesity risk. FTO and PPARG2 are relevant obesogenes. Our aim was to explore the effect of Pro12Ala (rs1801282) of PPARG2 and rs9939609 of FTO on obesity risk and to examine their interaction with lifestyle factors in an elderly population. Subjects (n = 978; aged 69 ± 6) were recruited from the SUN (Seguimiento Universidad de Navarra) Project. DNA was obtained from saliva, and lifestyle and dietary data were collected by validated self-reported questionnaires. Genotyping was assessed by RT-PCR plus allele discrimination. Subjects carrying the Ala allele of PPARG2 gene had a significantly increased obesity risk compared to non-carrier (Pro12Pro) subjects (OR, 1.66; 95  % CI, 1.01–2.74; p = 0.045). Greater obesity risk was also found in inactive or high carbohydrate intake subjects with the Ala12 allele of PPARG2 gene. Interestingly, subjects carrying the Ala allele of the PPARG2 gene and with a high CHO (>246 g/day) intake had an increased obesity risk compared to Pro12Pro subjects (OR, 2.67; 95 % CI, 1.3–5.46; p = 0.007; p for [CHO × PPARG2] interaction = 0.046). Moreover, in subjects with a high CHO intake, the co-presence of the Ala allele of PPARG2 gene and one minor A allele (rs9939609) of FTO gene did increase obesity risk (OR, 3.26; 95 % CI, 1.19–8.89; p = 0.021) when compared to non-carrier (Pro12Pro/TT) subjects. In conclusion, it appears that lifestyle factors may act as effect modifiers for obesity risk linked to Ala12 allele of the PPARG2 gene and the minor A allele of FTO gene in an elderly population.     

Preliminary findings on the influence of FTO rs9939609 and MC4R rs17782313 polymorphisms on resting energy expenditure,leptin and thyrotropin levels in obese non-morbid premenopausal women

Given that leptin, ghrelin and thyrotropin play a major role in the regulation of resting energy expenditure (REE) and that the FTO rs9939609 and the MC4R rs17782313 polymorphisms have been proposed to affect energy homeostasis, we hypothesized that both polymorphisms are associated with REE and that these relationships can be mediated by leptin, ghrelin and thyrotropin in obesity. Therefore, the present study aimed to examine the relationships between FTO rs9939609 and the MC4R rs17782313 with REE, leptin, ghrelin and thyrotropin levels in obese women. The study comprised 77 obese (body mass index 34.0?±?2.8 kg/m²) women (age 36.7?±?7 years). We measured body composition by dual-energy X-ray absorptiometry and REE by indirect calorimetry. We analysed fasting leptin, ghrelin and thyrotropin levels and the ratio of leptin to fat mass was calculated. Genotype distributions of the polymorphisms did not deviate from Hardy–Weinberg expectations (P values >0.2). Women carrying the A allele of the FTO rs9939609 had lower REE (1,580?±?22 vs. 1,739?±?35 kcal/day, P?<?0.001) and higher leptin to fat mass ratio (1.33?±?0.05 vs. 1.13?±?0.08 ng/ml kg, P?<?0.05) and thyrotropin levels (1.93?±?0.10 vs. 1.53?±?0.16 μU/ml, P?<?0.05) regardless of age and body mass index. We found no significant influence of the MC4R rs17782313 on energy metabolism or biochemical variables. Our findings confirm that the A allele of the FTO rs9939609 is associated with lower REE and increased plasma leptin levels. We also found an association between the FTO rs9939609 and thyrotropin, suggesting the possible influence of FTO in the hypothalamic–pituitary–thyroid axis as a potential mechanism of the increased adiposity.     

Meta‐analysis Added Power to Identify Variants in FTO Associated With Type 2 Diabetes and Obesity in the Asian Population

Several common variants in the intron 1 of FTO (fat mass and associated obesity) gene have been reliably associated with BMI and obesity in European populations. We analyzed two variants (rs9939609 and rs8050136) in 4,189 Chinese Han individuals and conducted a meta‐analysis of published studies in Asian population to investigate whether these variants are associated with type 2 diabetes (T2D) and obesity in Asian population. In this study, both the minor allele A of rs9939609 and the minor allele A of rs805136 were associated with increased risk of T2D, independent of measures of BMI; the odds ratios (ORs) per copy of the risk allele were 1.19 for rs9939609 (95% confidence interval (CI), 1.04–1.37; P = 0.01) and 1.22 for rs8050136 (95% CI, 1.07–1.40; P = 0.004) after adjusting for age, sex, and BMI. Our results also showed association with risk of obesity (rs9939609: OR = 1.39 (95% CI 1.04–1.85), P = 0.02; rs8050136: OR = 1.45 (95% CI 1.09–1.93), P = 0.01) but no association with overweight. These results were consistent with the pooled results from our meta‐analysis study (for diabetes, rs8050136, P = 1.3 × 10^?3; rs9939609, P = 9.8 × 10^?4; for obesity, rs8050136, P = 2.2 × 10^?7; rs9939609, P = 9.0 × 10^?9). Our findings indicate that the two variants (rs9939609 and rs8050136) in the FTO gene contribute to obesity and T2D in the Asian populations.     

Asociación de polimorfismos en el gen FTO con la obesidad mórbida en la población extremeña

ObjectiveTo select individuals whose morbid obesity can be attributed mainly to their individual genetic profile. After excluding patients with potential monogenic syndromes or diseases associated with obesity, we evaluated the association of the single nucleotide polymorphisms (SNPs) rs1861868 and rs9939609 of the fat-mass and obesity-associated FTO gene with an inherited predisposition to morbid obesity.Patients and methodsWe evaluated 270 patients with morbid obesity and onset before the age of 14 years and selected 194 due to their phenotypes and family history; 289 control individuals were included. The rs1861868 and rs9939609 variants, located in the FTO gene, were genotyped. Genotype and haplotype frequencies were compared between cases and controls.ResultsThe A allele of rs9939609 was associated with severe obesity starting in childhood among the Spanish population. The rs1861868 G/rs9939609 A haplotype of the FTO gene was also significantly associated with severe obesity in our population, with an odds ratio of 3.03 (95% confidence interval, 1.74–5.27).ConclusionAnalysis of the genetic basis of obesity requires rigorous selection of cases. In this study, the association of the rs9939609 SNP with obesity widely described in distinct populations was confirmed among overweight Spanish children. Genotyping rs1861868 allowed us to identify the first risk haplotype in the FTO gene, which is located in the adjacent haplotype block containing rs9939609. In-depth study of the variability of the FTO gene is essential to define its deleterious capacity.     

Common Variants of FTO Are Associated with Childhood Obesity in a Cross-Sectional Study of 3,126 Urban Indian Children

Background

FTO variants are robustly associated with obesity and related traits in many population and shown to have variable impact during life course. Although studies have shown association of FTO variants with adiposity in adult Indian, its association in Indian children is yet to be confirmed.

Methods

Here we examined association of FTO variants (rs9939609 and rs8050136) with obesity and related anthropometric and biochemical traits in 3,126 Indian children (aged 11–17 years) including 2,230 normal-weight and 896 over-weight/obese children. We also compared effects observed in the present study with that observed in previous studies on South Asian adults and children of other ethnic groups.

Results

The variant rs9939609 showed significant association with risk of obesity [OR = 1.21, P = 2.5×10⁻³] and its measures BMI, weight, waist circumference and hip circumference [β range = 0.11 to 0.14 Z-score units; P range = 1.3×10⁻⁴ to 1.6×10⁻⁷] in children. The observed effect sizes in Indian children were similar to those reported for European children. Variant rs9939609 explained 0.88% of BMI variance in Indian children. The effect sizes of rs9939609 on BMI and WC were ∼2 fold higher in children than adults. Interestingly rs9939609 was also associated with serum levels of thyroid stimulating hormone (TSH) [β = 0.10 Z-score, P = 5.8×10⁻³]. The other variant rs8050136 was in strong linkage disequilibrium with rs9939609 (r² = 0.97) and provided similar association results.

Conclusion

The study provides first report of association of FTO variants with obesity and related anthropometric traits in Indian children with higher impact in children compared to adults. We also demonstrated association of FTO variant with serum levels of TSH, indicating putative influence of FTO in hypothalamic-pituitary-thyroid axis.     

FTO at rs9939609, Food Responsiveness,Emotional Control and Symptoms of ADHD in Preschool Children

The FTO minor allele at rs9939609 has been associated with body mass index (BMI: weight (kg)/height (m)²) in children from 5 years onwards, food intake, and eating behaviour. The high expression of FTO in the brain suggests that this gene may also be associated with behavioural phenotypes, such as impulsivity and control. We examined the effect of the FTO minor allele (A) at rs9939609 on eating behaviour, impulsivity and control in young children, thus before the BMI effect becomes apparent. This study was embedded in the Generation R Study, a population-based cohort from fetal life onwards. 1,718 children of European descent were genotyped for FTO at rs9939609. With logistic regression assuming an additive genetic model, we examined the association between the FTO minor allele and eating behaviour, impulsivity and control in preschool children. There was no relation between FTO at rs9939609 and child BMI at this age. The A allele at rs9939609 was associated with increased food responsiveness (OR 1.21, p = 0.03). Also, children with the A allele were less likely to have symptoms of ADHD (OR 0.74, p = 0.01) and showed more emotional control (OR 0.64, p = 0.01) compared to children without the A allele. Our findings suggest that before the association between FTO and BMI becomes apparent, the FTO minor allele at rs9939609 leads to increased food responsiveness, a decreased risk for symptoms of ADHD and better emotional control. Future studies are needed to investigate whether these findings represent one single mechanism or reflect pleiotropic effects of FTO.     

Rs7206790 and rs11644943 in FTO Gene Are Associated with Risk of Obesity in Chinese School-Age Population

To evaluate the associations between candidate FTO single nucleotide polymorphisms (SNPs) and obesity, a case-control study was conducted among Chinese school-age children, which included 500 obese cases and 500 matched controls (age, gender and location). We selected 24 candidate FTO tag-SNPs via bio-informatics analysis and performed genotyping using SNPScan technology. Results indicated that rs7206790 and rs11644943 were significantly associated with obesity among school-age children in both additive and recessive models (P<0.05) after adjusting confounders. Comparing rs7206790 CC and CG genotype of carriers, those carrying the GG genotype had an increased risk of obesity (adjusted odds ratio [OR], 3.76; 95% Confidence interval [CI], 1.24–11.43). Carriers of the AA allele of rs11644943 had a lower risk of obesity (adjusted OR, 0.16; 95% CI, 0.04–0.72) compared with those of the T allele (TT and TA). These two SNPs (rs7206790 and rs11644943) were not Linkage Disequilibrium (LD) with previous reported obesity-associated SNPs. Under the recessive model adjusted for age and gender and location, rs7206790 GG allele carriers had significantly increased BMIs (P = 0.012), weight (P = 0.012), waist circumferences (WC) (P = 0.045) and hip circumferences (HC) (P = 0.033). Conversely, rs11644943 AA allele carriers had significantly decreased BMIs (P = 0.006), WC (P = 0.037) and Waist-to-height ratios (WHtR) (P = 0.012). A dose-response relationship was found between the number of risk alleles in rs7206790, rs11644943 and rs9939609 and the risk of obesity. The Genetic Risk Score (GRS) of the reference group was 3; in comparison, those of 2, 4, and ≥5 had ORs for obesity of 0.24 (95%CI, 0.05–1.13), 1.49 (95%CI, 1.10–2.01), and 5.20 (95%CI, 1.75–15.44), respectively. This study confirmed the role of FTO variation on genetic susceptibility to obesity. We reported two new obesity-related FTO SNPs (rs7206790 and rs11644943) among Chinese school-age children.     

The Common Variant in the FTO Gene Did Not Modify the Effect of Lifestyle Changes on Body Weight: The Finnish Diabetes Prevention Study

The common single‐nucleotide polymorphism in the FTO (fat mass and obesity associated) gene is consistently associated with an increased risk of obesity. However, the knowledge of a potential modifying effect of the FTO gene on changes in body weight achieved by lifestyle intervention is limited. We examined whether the FTO gene variant (rs9939609, T/A) is associated with body weight and BMI and long‐term weight changes in the Finnish Diabetes Prevention Study (DPS). Altogether, 522 (aged 40–65 years; BMI ≥25 kg/m²) subjects with impaired glucose tolerance (IGT) were randomized to control and lifestyle intervention groups. SNP rs9939609 was genotyped from 502 subjects. At baseline, those with the AA genotype had higher BMI than subjects with other genotypes (P = 0.006). The association was observed in women (P = 0.016) but not in men. During the 4‐year follow‐up, the subjects with the AA genotype had consistently the highest BMI (P = 0.009) in the entire study population. The magnitude of weight reduction was greater in the intervention group, but the risk allele did not modify weight change in either of the groups. Our results confirm the association between the common FTO variant and BMI in a cross‐sectional setting and during the long‐term lifestyle intervention. We did not observe association between FTO variant and the magnitude of weight reduction achieved by long‐term lifestyle intervention. Based on the results from the DPS, it is unlikely that the common variant of the FTO gene affects the success of lifestyle modification on weight loss.     

The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women

Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR)  = 1.17; 95% confidence interval (CI): 1.03–1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91–1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.     

Age- and Sex-Dependent Association between FTO rs9939609 and Obesity-Related Traits in Chinese Children and Adolescents

Background

The associations between common variants in the fat mass- and obesity-associated (FTO) gene and obesity-related traits may be age-dependent and may differ by sex. The present study aimed to assess the association of FTO rs9939609 with body mass index (BMI) and the risk of obesity from childhood to adolescence, and to determine the age at which the association becomes evident.

Methods

Totally 757 obese and 2,746 non-obese Chinese children aged 6–18 years were genotyped for FTO rs9939609. Of these, a young sub-cohort (n = 777) aged 6–11 years was reexamined 6 years later. Obesity was defined using the sex- and age-specific BMI cut-offs recommended by the International Obesity Task Force.

Results

The associations of FTO rs9939609 with BMI and obesity did not appear until children reached 12–14 years. The variant was associated with an increased BMI in boys (β = 1.50, P = 0.004) and girls (β = 0.97, P = 0.018), respectively. Thereafter, the magnitude of association increased in girls at ages 15–18 years (β = 2.02, P<0.001), but not boys (β = 0.10, P>0.05). Age was found to interact with the variant on BMI (P<0.001) and obesity (P = 0.042) only in girls. In the sub-cohort, the associations of FTO rs9939609 with BMI (β = 1.07, P = 0.008) and obesity (OR = 2.09, 95% CI: 1.12, 3.91) were only observed 6 years later (ages 12–18 years) in girls, even after adjusting for baseline BMI.

Conclusions

The association between FTO rs9939609 and obesity-related traits may change from childhood to adolescence in Chinese individuals, and the association may start as early as age 12 years, especially in girls.     

Analysis of FTO gene variants with measures of obesity and glucose homeostasis in the IRAS Family Study

Multiple studies have identified FTO gene variants associated with measures of adiposity in European-derived populations. The objective of the study was to determine whether FTO variants were associated with adiposity, including visceral and subcutaneous adipose tissue (VAT, SAT), and glucose homeostasis measures in the Insulin Resistance Atherosclerosis Family Study (IRASFS). A total of 27 SNPs in FTO intron 1, including SNPs prominent in the literature (rs9939609, rs8050136, rs1121980, rs17817449, rs1421085, and rs3751812), were genotyped in 1,424 Hispanic Americans and 604 African Americans. Multiple SNPs were associated with BMI and SAT (P values ranging from 0.001 to 0.033), and trending or associated with waist circumference (P values ranging from 0.008 to 0.099) in the Hispanic Americans. No association was observed with VAT, illustrating that FTO variants are associated with overall fat mass instead of specific fat depots. For the glucose homeostasis measures, variants were associated with fasting insulin but, consistent with other studies, after BMI adjustment, no evidence of association remained. The lack of association of FTO SNPs with insulin sensitivity is consistent with the lack of association with VAT, since these traits are strongly correlated. In the African Americans, only rs8050136 and rs9939609 were associated with BMI and WAIST (P values of 0.011 and 0.034), and associated or trending towards association with SAT (P values of 0.038 and 0.058). These results confirm that FTO variants are associated with adiposity measures, predisposing individuals to obesity by increasing overall fat mass in Hispanic Americans and to a lesser degree in African Americans.     

Detailed analysis of variants in FTO in association with body composition in a cohort of 70-year-olds suggests a weakened effect among elderly

Background

The rs9939609 single-nucleotide polymorphism (SNP) in the fat mass and obesity (FTO) gene has previously been associated with higher BMI levels in children and young adults. In contrast, this association was not found in elderly men. BMI is a measure of overweight in relation to the individuals'' height, but offers no insight into the regional body fat composition or distribution.

Objective

To examine whether the FTO gene is associated with overweight and body composition-related phenotypes rather than BMI, we measured waist circumference, total fat mass, trunk fat mass, leg fat mass, visceral and subcutaneous adipose tissue, and daily energy intake in 985 humans (493 women) at the age of 70 years. In total, 733 SNPs located in the FTO gene were genotyped in order to examine whether rs9939609 alone or the other SNPs, or their combinations, are linked to obesity-related measures in elderly humans.

Design

Cross-sectional analysis of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort.

Results

Neither a single SNP, such as rs9939609, nor a SNP combination was significantly linked to overweight, body composition-related measures, or daily energy intake in elderly humans. Of note, these observations hold both among men and women.

Conclusions

Due to the diversity of measurements included in the study, our findings strengthen the view that the effect of FTO on body composition appears to be less profound in later life compared to younger ages and that this is seemingly independent of gender.     

Prospective Analysis of the Association of a Common Variant of FTO (rs9939609) with Adiposity in Children: Results of the IDEFICS Study

Objectives

We investigated cross-sectionally and longitudinally the relationship between FTO rs9939609 and obesity-related characteristics in the European children of the IDEFICS project and the interaction of this variant with a lifestyle intervention.

Population and Methods

A cohort of 16224 children (2–9 years) was recruited into a population-based survey (T0) from eight European countries. A second survey (T1) reassessed the children two years later. A random sample of 4405 children was extracted for genetic studies. 3168 children were re-examined two years later. Half of them underwent a lifestyle intervention program. The FTO rs9939609 was genotyped. Weight, height, waist circumference, triceps and subscapular skinfolds were measured at T0 and T1.

Results

At T0, the risk A allele of rs9939609 was significantly associated with higher values of body mass index (BMI), waist circumference and skinfolds (age, sex, and country-adjusted p-values: all p<0.001) and with a statistically significant increased risk of overweight/obesity.Over the two year follow-up, no interaction between genotype and intervention was observed. The A allele was associated to a significantly higher increase in all the anthropometric variables examined at T0 independently from the study group (intervention versus control) (p-values: all p<0.002, adjusted for age, sex, country, intervention/control study group, T0 values, and individual time interval between T0 and T1). Over the two-year follow–up, 210 new cases of overweight/obesity occurred. A statistically significant higher incidence of overweight/obesity was associated to the A allele [OR_A = 1.95, 95% CI = (1.29; 2.97)].

Conclusions

We confirmed the association between the FTO rs9939609 and body mass and overweight/obesity risk in European children. The main finding of the study is that the A allele carriers present higher increase of body mass and central adiposity over time and higher risk of developing overweight/obesity during growth, independently from intervention measures.     

The rs9939609 polymorphism in the fat mass and obesity associated (FTO) gene is associated with obesity in Tunisian population

Abstract

Context: Variations in the fat mass and obesity-associated gene (FTO) has been associated with obesity in many populations, but the results are conflicting.

Objective: The aim of this study was to evaluate the effect of the rs9939609 polymorphism in the FTO gene on obesity risk and plasma leptin, adiponectin, insulin and lipid concentrations in Tunisians.

Materials and methods: Four hundred and ninety-four subjects with obesity and 334 non-obese participated in this study. The rs9939609 (T/A) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: Significant differences in genotype frequencies were observed between cases and controls. In the separate analysis by gender, the association between the AA genotype and obesity was statistically significant in women but not in men. After stratification by obesity class this association remains only with obesity class III.

Discussion: Our study is in agreement with studies on Caucasian, Portuguese and Cebu Filipino populations where a gender-specific association was found between rs9939609 polymorphism and obesity. It is also in agreement with studies on Mexican, Spanish and European populations, where an association was found with obesity class III.

Conclusion: The rs9939609 polymorphism of FTO gene is associated with obesity, especially obesity class III in women.     

Polymorphisms in FTO and near TMEM18 associate with type 2 diabetes and predispose to younger age at diagnosis of diabetes

Variations in the FTO gene and near the TMEM18 gene are risk factors for common form of obesity, but have also been linked with type 2 diabetes (T2D). Our aim was to investigate the contribution of these variants to risk of T2D in a population in Latvia. Four single nucleotide polymorphisms (SNP) in the first and fourth intronic regions of FTO and one close to TMEM18 were genotyped in 987 patients with T2D and 1080 controls selected from the Latvian Genome Data Base (LGDB). We confirmed association of SNPs in the first intron (rs11642015, rs62048402 and rs9939609) of FTO and rs7561317 representing the TMEM18 locus with T2D. Association between SNP in FTO and T2D remained significant after correction for body mass index (BMI). The rs57103849 located in the fourth intron of FTO and rs7561317 in TMEM18 showed BMI independent association with younger age at diagnosis of T2D. Our results add to the evidence that BMI related variants in and near FTO and TMEM18 may increase the risk for T2D not only through secondary effects of obesity. The influence of variants in the fourth intron of the FTO gene on development of T2D may be mediated by mechanisms other than those manifested by SNPs in the first intron of the same gene.     

Inverse Association between Obesity Predisposing FTO Genotype and Completed Suicide

The A allele of rs9939609 in the FTO gene predisposes to increased body mass index (BMI) and obesity. Recently we showed an inverse association between the obesity related A allele of rs9939609 and alcohol dependence which was replicated by others. Since this finding raises a possibility that FTO may be associated with other psychiatric phenotypes, we aimed to examine association of rs9939609 with completed suicide. We genotyped rs9939609 in 912 suicide victims and 733 controls using TaqMan approach. We observed an inverse association between suicide and the rs9939609 A allele (OR = 0.80, P = 0.002, P_cor = 0.006) with genotype distribution suggesting a co-dominant effect. Given the link between alcoholism and suicide under influence of alcohol reported in Polish population, confounding by alcohol addiction was unlikely due to apparently similar effect size among cases who were under influence of ethanol at the time of death (OR = 0.76, P = 0.003, N = 361) and those who were not (OR = 0.80, P = 0.007, N = 469). The search for genotype-phenotype correlations did not show significant results. In conclusion, our study proves that there is an inverse association between rs9939609 polymorphism in FTO gene and completed suicide which is independent from association between FTO and alcohol addiction.