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

Kalniņa, Ineta; Zaharenko, Linda; Vaivade, Iveta; Rovīte, Vita; Ņikitina-Zaķe, Liene; Pečulis, Raitis; Fridmanis, Dāvids; Geldnere, Kristine; Jacobsson, Josefin A.; Almén, Markus Sällman; Pīrāgs, Valdis; Schiöth, Helgi B.; Kloviņš, Jānis

doi:10.1016/j.gene.2013.06.079

Cited by 27 publications

(26 citation statements)

References 55 publications

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“…Interestingly, ten of the identified SNPs have a stronger association than the commonly studied rs9939609, and rs62048402 has been shown to be the most significant one. 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.…”

Section: Fto and Obesity In Different Ethnic Groupssupporting

confidence: 72%

“…A recent study in a Latvian population confirmed the association of SNPs in the first intron (rs11642015, rs62048402 and rs9939609) of FTO with T2D, which remained significant after correction for BMI. Interestingly, the rs57103849 showed BMI independent association with younger age T2D diagnosis [18]. The rs57103849, which lies in the fourth intron outside the FTO gene cluster associated with obesity, was reported to correlate with insulin resistance independently of BMI [46].…”

Section: Fto and Diabetesmentioning

confidence: 97%

“…Meta-analyses [8,15] [7,[12][13][14][15], which seemed to have the strongest influence on BMI mainly because of its prevalence -45% for allele A due to HapMap. Only a few studies have referred to other introns -two, three [16], eight [17] and four [18].…”

Section: Fto and Obesity In Different Ethnic Groupsmentioning

confidence: 99%

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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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Section: Fto and Obesity In Different Ethnic Groupssupporting

confidence: 72%

Section: Fto and Diabetesmentioning

confidence: 97%

See 1 more Smart Citation

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

Zdrojowy-Wełna¹,

Tupikowska²,

Kolačkov³

et al. 2014

Endokrynologia Polska

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“…Genome-wide association studies (GWAS) have identified risk alleles in/near TMEM18, associated with body mass index (BMI) (Thorleifsson et al 2009, Willer et al 2009 and type 2 diabetes (Kalnina et al 2013). TMEM18 is ubiquitously expressed throughout the body and central nervous system-including the hypothalamus and other…”

Section: Introductionmentioning

confidence: 99%

The Drosophila ortholog of TMEM18 regulates insulin and glucagon-like signaling

Wiemerslage

Gohel

Maestri

et al. 2016

Journal of Endocrinology

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Transmembrane protein 18 (TMEM18) is an ill-described, obesity-related gene, but few studies have explored its molecular function. We found single-nucleotide polymorphism data, suggesting that TMEM18 may be involved in the regulation/physiology of metabolic syndrome based on associations with insulin, homeostatic model assessment-β (HOMAβ), triglycerides, and blood sugar. We then found an ortholog in the Drosophila genome, knocked down Drosophila Tmem18 specifically in insulin-producing cells, and tested for its effects on metabolic function. Our results suggest that TMEM18 affects substrate levels through insulin and glucagon signaling, and its downregulation induces a metabolic state resembling type 2 diabetes. This work is the first to experimentally describe the metabolic consequences of TMEM18 knockdown, and further supports its association with obesity. 233-243TMEM18 regulates insulin and glucagon l wiemerslage and others

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“…Associations with chromosomal areas, with ethnicity, with FTO and interleukins have been reported [10][11][12][13]. ACP 1 could be a candidate gene for T2D with a significant role in the clinical manifestations of the disease including blood glycemic level, coronary artery disease [14] and age at the onset.…”

mentioning

confidence: 98%