Determination of the obesity-associated gene variants within the entire FTO gene by ultra-deep targeted sequencing in obese and lean children

Almén, Markus Sällman; Rask‐Andersen, Mathias; Jacobsson, Josefin A.; Ameur, Adam; Kalniņa, Ineta; Moschonis, George; Juhlin, Sofie; Bringeland, Nathalie; Hedberg, Lilia; Ignatovica, Vita; Chrousos, George P.; Μanios, Yannis; Kloviņš, Jānis; Marcus, Claude; Gyllensten, Ulf; Fredriksson, Robert; Schiöth, Helgi B.

doi:10.1038/ijo.2012.57

Cited by 33 publications

(33 citation statements)

References 32 publications

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“…But our study showed that rs62048402 had a lower odds ratio (OR = 1.259, 95% CI = 1.016-1.560, P = 0.035) than rs9939609 (OR = 1.322, 95% CI = 1.067-1.637, P = 0.011). In Sällman Almén's study (9), rs9939609 and rs62048402 was in a linkage disequilibrium (LD) with r 2 value of 0.87 among Swedish children. The r 2 value was 0.96 in our Chinese population, indicating LD of the two FTO SNPs among Chinese population was stronger than that of European population.…”

Section: Association Of Eight Variants With Obesitymentioning

confidence: 99%

“…All the two SNPs were within intron 1 of FTO (15). Sällman et al (9) found that the intron 1 is the only region within FTO associated with obesity, and reported that rs62048402 (OR = 1.35, 95% CI = 1.13-1.60, P < 0.0007) had a stronger association with obesity than SNP rs9939609 (OR = 1.25, 95% CI = 1.05-1.48, P < 0.012). But our study showed that rs62048402 had a lower odds ratio (OR = 1.259, 95% CI = 1.016-1.560, P = 0.035) than rs9939609 (OR = 1.322, 95% CI = 1.067-1.637, P = 0.011).…”

Section: Association Of Eight Variants With Obesitymentioning

confidence: 99%

“…The strongest associated marker was SNP rs2967951 in rhophilin-associated tail protein 1-like (ROPN1L) located at 5p15.2. Moreover, in 2013, Sällman et al (9) identified SNP rs62048482 in intron 1 of fat mass and obesity-associated gene (FTO) in Swedish children, having stronger association with obesity than SNP rs9939609, although the association between FTO rs9939609 and obesity had been widely confirmed (10,11).…”

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confidence: 99%

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Association study of childhood obesity with eight genetic variants recently identified by genome-wide association studies

Meng

Song

et al. 2014

Pediatr Res

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Background:Being overweight or obese is becoming increasingly common in low-and middle-income countries. The present study aimed to examine association of eight genetic variants with obesity and to estimate the cumulative effects of these variants in Chinese children. Methods:We conducted the case-control study in a total of 2,030 subjects. Genotyping of seven novel variants was performed with matrix-assisted laser desorption ionization time of flight mass spectrometry, while rs9939609 was genotyped with tetra-primer amplification refractory mutation system analysis. results: The association of two fat mass and obesityassociated gene (FTO) single-nucleotide polymorphisms (SNPs; rs9939609 and rs62048402) with body mass index (BMI) or obesity reached nominal significance at P < 0.05. We found a cumulative effect of five SNPs on the risk of overweight and obesity (odds ratio (OR) = 1.197, 95% confidence interval (CI) = 1.068-1.342, P = 0.002). Subjects carrying 9 or more effect alleles had a 127% increased risk of overweight and obesity (OR = 2.270, 95% CI = 1.403-3.671, P = 0.001) compared with subjects who carry 6 or fewer effect alleles. conclusion: We confirmed two FTO SNPs (rs62048402 and rs9939609) had nominal significant effects on BMI or obesity. We identified the cumulative effect of five SNPs on risk of overweight and obesity. The results provided evidence for identifying genetic factors related to childhood obesity.

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Section: Association Of Eight Variants With Obesitymentioning

confidence: 99%

Section: Association Of Eight Variants With Obesitymentioning

confidence: 99%

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confidence: 99%

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Association study of childhood obesity with eight genetic variants recently identified by genome-wide association studies

Meng

Song

et al. 2014

Pediatr Res

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“…Recently however, results of a new study have been released in which the entire FTO gene in total 412 Kbp has been amplified in a group of 524 morbid obese and 527 lean Swedish children [19]. This is the first comprehensive variation map of the FTO gene, including both SNPs and small indels (small deletions and insertions), using new generation sequencing of pooled DNA -massive parallel sequencing (SOLiD).…”

Section: Fto and Obesity In Different Ethnic Groupsmentioning

confidence: 99%

“…This was confirmed in a recent study on a Latvian population [18] where SNPs rs62048402, rs9939609 and rs7561317 were associated with higher BMI with p-values of 0.0036, 0.0069 and 0.015 respectively. The four top obesity-associated SNPs in a study by Almen et al [19], with rs62048402 being the strongest one, lie within the potential regulatory region of intron one. Some transcription factors, such as the glucocorticosteroid receptor, bind there and this is the only known functional region of the comprehensive FTO map which may potentially explain the pathomechanism of related obesity.…”

Section: Fto and Obesity In Different Ethnic Groupsmentioning

confidence: 99%

Rola genu podatności na otyłość (FTO) w rozwoju otyłości — przegląd

Zdrojowy-Wełna¹,

Tupikowska²,

Kolačkov³

et al. 2014

Endokrynologia Polska

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Obesity is an epidemic of the 21st century. The magnitude of this problem stems from its increasing prevalence and numerous metabolic complications caused by excessive fat accumulation. The pathogenesis involves both environmental and genetic factors, and FTO (fat mass and obesity-associated gene) is one of the most significant among genes predisposing to obesity. The role of FTO polymorphism in the development of obesity has been confirmed in many studies, but the effect varies significantly in different ethnic groups. Moreover, the exact mechanisms of FTO influence are yet to be explained. The association between FTO and lifestyle factors such as diet and physical activity has been extensively studied in recent years. This paper presents current knowledge about the role of FTO gene in the development of obesity and type 2 diabetes in different ethnic groups and the association between FTO polymorphism and lifestyle modifications predisposing to adiposity. StreszczenieOtyłość jest epidemią XXI wieku. Znaczenie tego problemu wynika zarówno z jego narastającej częstości, jak i wielu powikłań zdrowotnych, którym sprzyja nadmiar tkanki tłuszczowej. W patogenezie otyłości istotną rolę odgrywają czynniki środowiskowe i genetyczne, a spośród tych ostatnich jednym z najbardziej znaczących jest gen FTO (gen podatności na otyłość). Wpływ polimorfizmu FTO na rozwój otyłości potwierdzono w wielu pracach, lecz jego bezpośredni efekt zależy od pochodzenia etnicznego osób badanych. Ponadto wciąż niejasny jest dokładny mechanizm działania tego genu. W ostatnich latach intensywnie badano związek polimorfizmu genu FTO ze środowiskowymi czynnikami ryzyka otyłości, takimi jak dieta i wysiłek fizyczny. W niniejszej pracy przedstawiono obecny stan wiedzy o roli genu FTO w rozwoju otyłości i cukrzycy typu 2 w różnych grupach etnicznych oraz jego związek ze stylem życia, który predysponuje do nadmiernego gromadzenia tkanki tłuszczowej.

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The association between sarcopenia susceptibility and polymorphisms of FTO, ACVR2B, and IRS1 in Tibetans

Zhang¹,

Li³

et al. 2021

Molec Gen & Gen Med

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Background Hypoxia within the plateau has a negative effect on skeletal muscle and may play a role in the development of sarcopenia in humans. Tibetans having lived in the Qinghai‐Tibet Plateau for thousands of years, are a high‐risk group for sarcopenia; however, they have a distinctive suite of genetic traits that enable them to tolerate environmental hypoxia and are genetically significantly different from Han Chinese and other lowland populations. Sarcopenia has been consistently found to be associated with single‐nucleotide polymorphisms, but few studies have investigated the role of single‐nucleotide polymorphisms in a range of muscle phenotypes and sarcopenia in Tibetan peoples. Methods Our study aimed to investigate the skeletal muscle mass and fat mass of 160 Tibetans (80 men and 80 women) from Lhasa (altitude of 3600 meters) and analyze the association between the polymorphisms of fat mass and obesity protein (FTO) rs9939609, FTO rs9936385, activin type IIB receptor (ACVR2B) rs2276541, insulin receptor substrate 1 (IRS1) 2943656 and sarcopenia. Result FTO rs9939609 and rs9936385 polymorphisms were associated with lower limb skeletal muscle mass and sarcopenia for Tibetan women, and TT homozygotes had a higher risk for sarcopenia. But ACVR2B rs2276541 and IRS1 2943656 polymorphisms were unassociated with sarcopenia in Tibetan. Conclusion In Tibetans, FTO rs9939609 and rs9936385 polymorphisms were associated with sarcopenia, and ACVR2B rs2276541 and IRS1 2943656 polymorphisms were unassociated with sarcopenia.

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Determination of the obesity-associated gene variants within the entire FTO gene by ultra-deep targeted sequencing in obese and lean children

Cited by 33 publications

References 32 publications

Association study of childhood obesity with eight genetic variants recently identified by genome-wide association studies

Association study of childhood obesity with eight genetic variants recently identified by genome-wide association studies

Rola genu podatności na otyłość (FTO) w rozwoju otyłości — przegląd

The association between sarcopenia susceptibility and polymorphisms of FTO, ACVR2B, and IRS1 in Tibetans

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