<i>FTO</i> genetic variants and risk of obesity and type 2 diabetes: A meta‐analysis of 28,394 Indians

Vasan, Senthil K.; Karpe, Fredrik; Gu, Harvest F.; Brismar, Kerstin; Fall, Caroline; Ingelsson, Erik; Fall, Tove

doi:10.1002/oby.20606

Cited by 41 publications

(33 citation statements)

References 39 publications

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“…Similar results were found in Indian, American and Chinese populations [4, 10, 23]. Vasan and colleagues [24] provided evidence that FTO -T2DM risk -among Asian Indians- was attenuated but not fully abolished when adjusting to BMI. In contrast, a recent study conducted in Kuwaiti population did not observe an association between the FTO rs9939609 with T2DM risk [25].…”

Section: Discussionsupporting

confidence: 68%

Common FTO rs9939609 variant and risk of type 2 diabetes in Palestine

et al. 2018

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BackgroundGenetic and environmental factors play a crucial role in the development of type 2 diabetes mellitus (T2DM) and obesity. This study aimed to investigate the association of the fat-mass and obesity-associated gene (FTO) rs9939609 variant with T2DM and body mass index (BMI) among Palestinian population.MethodsA total of 399 subjects were recruited, of whom 281 were type 2 diabetic patients and 118 normoglycemic subjects. All of them were unrelated, aged > 40 years and recruited within the period 2016–2017. The A allele of FTO rs9939609 was identified by PCR–RFLP.ResultsSignificant association of the minor allele A of FTO rs9939609 and T2DM risk was observed with an allelic odd ratio of 1.92 (95% CI [1.09–3.29], p = 0.02) adjusted for age and gender, this association partly attenuated when adjusted for BMI with OR of 1.84, (95%CI [1.04–3.05], p = 0.03). Stratified data by glycemic status across FTO genotypes showed that A allele was marginally associated with increased BMI among diabetic group (p = 0.057) but not in control group (p = 0.7). Moreover, no significant association was observed between FTO genotypes and covariates of age, gender, T2DM complications or any tested metabolic trait in both diabetic and nondiabetic individuals (p > 0.05).ConclusionsThe variant rs9939609 of the FTO gene was associated with T2DM in Palestine. This is the first study conducted on this gene in the Palestinian population and provides valuable information for comparison with other ethnic groups. Further analysis with larger sample size is required to elucidate the role of this variant on the predisposition to increased BMI in Palestinians.

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Section: Discussionsupporting

confidence: 68%

Common FTO rs9939609 variant and risk of type 2 diabetes in Palestine

et al. 2018

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“…Insulin resistance is often related to obesity, and several studies have demonstrated that the association of ENPP1 and FTO polymorphisms with T2DM is mediated by obesity 8,9,45,46 . However, our study failed to show any association between ENPP1, FTO and obesity.…”

Section: Discussionmentioning

confidence: 99%

“…The first surge of T2DM GWA identified among others the fat mass and obesity-associated gene (FTO), which is the strongest obesity genetic risk factor reported so far 6,7 . It has been shown to confer susceptibility to T2DM in the presence 8,9 and absence of obesity 10,11 . The most widely studied SNP of the ENPP1, K121Q (rs1044498), has produced conflicting results in relation to T2DM susceptibility [12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

et al. 2016

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Background: Transcription factor 7-like 2 gene (TCF7L2), fat mass and obesity-associated gene (FTO), and ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) are known risk loci for type 2 diabetes (T2DM) mostly in European populations. Objectives: To assess the association of these genes with T2DM risk in a South African mixed-ancestry population. Methods: Five hundred and sixty six participants were genotyped for ENPP1-rs997509 and -rs1044498, FTO-9941349 and -rs3751812, TCF7L2-rs12255372 and -rs7903146 polymorphisms using Taqman genotyping assays and validated by automated sequencing to assess the association of the polymorphisms with cardiometabolic traits. Results: In logistic regression models adjusted for age, sex, body mass index (BMI) and insulin resistance, minor allele of rs997509 was associated with a higher risk of prevalent T2DM under a recessive model [odd ratio 4.60 (95% confidence interval: 1.07 to 19.86); p = 0.040].Under additive model, the rs7903146 [1.43 (1.00 to 2.04); p= 0.053] and rs9941349 [1.43 (1.00 to 2.04); p = 0.052] minor alleles showed marginally significant associations with a high risk of T2DM. However, only the rs7903146 alleles (p=0.011) and genotypes (p=0.025) distributions were statistically significantly different between diabetic and non-diabetic individuals. Conclusion: Our findings demonstrate that ENPP1, TCF7L2, and FTO may predispose to T2DM in the mixed-ancestry population.

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“…Based on parental report, participants were 85.9% white and non-Hispanic, 1.3% white and Hispanic, and 5.1% unknown race and Hispanic, with the remainder (7.7%) being non-white and non-Hispanic. Because previously reported associations between the FTO genotype and obesity-related phenotypes are commonly observed across populations with divergent ancestral origins (34,35), we conducted a sensitivity analysis restricted to non-Hispanic white participants to account for potential confounding by population stratification (36).…”

Section: Methodsmentioning

confidence: 99%

Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues

Rapuano

Zieselman

Kelley

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Obesity is a major public health concern that involves an interaction between genetic susceptibility and exposure to environmental cues (e.g., food marketing); however, the mechanisms that link these factors and contribute to unhealthy eating are unclear. Using a well-known obesity risk polymorphism (FTO rs9939609) in a sample of 78 children (ages 9-12 y), we observed that children at risk for obesity exhibited stronger responses to food commercials in the nucleus accumbens (NAcc) than children not at risk. Similarly, children at a higher genetic risk for obesity demonstrated larger NAcc volumes. Although a recessive model of this polymorphism best predicted body mass and adiposity, a dominant model was most predictive of NAcc size and responsivity to food cues. These findings suggest that children genetically at risk for obesity are predisposed to represent reward signals more strongly, which, in turn, may contribute to unhealthy eating behaviors later in life.T he relationship between genes and sensitivity to environmental cues is elusive, yet it is paramount to understanding the development of potentially maladaptive human behaviors. The rising prevalence of obesity is a major public health concern that has been attributed to various factors, such as genetic susceptibility (1), and increases in the availability and marketing of calorie-dense foods (2). However, little is known about how genetic predisposition to obesity influences sensitivity to real-world food cues and contributes to the development of unhealthy eating behaviors.Previous neuroimaging studies have demonstrated that responses to food cues in reward-related regions of the brain, such as the nucleus accumbens (NAcc), predict weight gain in adulthood (3) and giving in to food temptations in daily life (4). Furthermore, structural differences in NAcc volume have been positively associated with body mass index (BMI) in adults (5, 6). Because the development of the NAcc precedes the development of prefrontal control systems (7), this structure is suggested to play a key role in motivating and establishing unhealthy eating behaviors early in the lifespan. Importantly, genetic factors are a known contributor to brain development (8) and may influence risky behaviors during childhood and adolescence by biasing the early development of anatomical structures underlying reward-related brain function.In addition, the notion that genes contribute to obesity has recently gained much attention. More specifically, the fat-mass and obesity-associated (FTO) rs9939609 polymorphism has been strongly related to increased BMI and adiposity across the lifespan, and is suggested to influence food intake and food choice, rather than energy expenditure (9-11). Those with two high-risk "A" alleles (AA) are at an enhanced risk for obesity compared with those with two low-risk "T" alleles (TT) or those who are heterozygous (AT) for the FTO rs9939609 polymorphism. Although the FTO gene is highly expressed in the brain (1), the mechanism by which this gene promotes unhealthy...

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FTO genetic variants and risk of obesity and type 2 diabetes: A meta‐analysis of 28,394 Indians

Cited by 41 publications

References 39 publications

Common FTO rs9939609 variant and risk of type 2 diabetes in Palestine

Common FTO rs9939609 variant and risk of type 2 diabetes in Palestine

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues

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