Association between the FTO rs9939609 polymorphism and the metabolic syndrome in a non-Caucasian multi-ethnic sample

Al-Attar, Salam A.; Pollex, Rebecca L.; Ban, Matthew R.; Young, T. Kue; Bjerregaard, Peter; Anand, Sonia S.; Yusuf, Salim; Zinman, Bernard; Harris, Stewart B.; Hanley, Anthony J.; Connelly, Philip W.; Huff, Murray W.; Hegele, Robert A.

doi:10.1186/1475-2840-7-5

Cited by 89 publications

(70 citation statements)

References 14 publications

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“…Within the past year exciting new evidence from genome-wide association studies reproducibly highlighted the FTO SNP allelic distribution as a predictive factor for obesity in various human populations (Dina et al 2007, Al-Attar et al 2008, Freathy et al 2008, Hotta et al 2008, Hubacek et al 2008, Willers et al 2008). The mechanisms underlying the physiological relationship between FTO allelic variations and alterations of body weight homeostasis are yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression

Sebért¹,

Hyatt²,

Chan³

et al. 2010

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The recent discovery of an association between body composition, energy intake and the fat mass and obesity-associated (FTO) gene represents a promising new therapeutic target in obesity prevention. In a well, pre-established large animal model, we investigated the regulation of FTO gene expression under conditions either leading to obesity or increased risk of obesity related disorders: i) a sedentary 'Western' lifestyle and ii) prenatal exposure to nutrient restriction. Pregnant sheep were either fed to fully meet their nutritional requirements throughout gestation or 50% of this amount from early-to-mid gestation. Following weaning, offspring were either made obese through exposure to a sedentary obesogenic environment or remained lean. A significant positive relationship between placental FTO gene expression and fetal weight was found at 110 days gestation. In both the newborn and adult offspring, the hypothalamus was the major site of FTO gene expression. Hypothalamic FTO gene expression was upregulated by obesity and was further increased by prenatal nutrient restriction. Importantly, we found a strong negative relationship between the hypothalamic FTO gene expression and food intake in lean animals only that may imply FTO as a novel controller of energy intake. In contrast, FTO gene expression in the heart was downregulated in obese offspring born to nutrient restricted mothers. In addition, FTO gene expression was unaffected by obesity or prenatal diet in insulin-dependent tissues, where it changed with age possibly reflecting adaptations in cellular energetic activity. These findings extend information gained from human epidemiology and provide new insights into the regulation of in vivo energy metabolism to prevent obesity.

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Section: Discussionmentioning

confidence: 99%

Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression

Sebért¹,

Hyatt²,

Chan³

et al. 2010

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“…However, the genetic urate score analysis did not provide evidence for an association between serum urate and cardiovascular risk factors or coronary heart disease (Yang et al, 2010). FTO, encoding a nuclear protein of the AlkB-related non-heme iron and 2-oxoglutarate-dependent oxygenase superfamily, was identified as an obesity-related gene, and which increased obesity-related vascular diseases (Al-Attar et al, 2008). PCAF has histone acetylating activity, promotes transcription of multiple inflammatory genes, and acts as master switch that stimulates multiple inflammatory processes.…”

Section: Discussionmentioning

confidence: 99%

“…FTO was identified through its relationship to obesity, which increased risk of obesityrelated vascular diseases (Al-Attar et al, 2008). Individuals with an FTO polymorphism were shown to have a trend towards increased intima-medial thickness of the carotid artery, which is a clinical marker of atherosclerosis (Kivimaki et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Intracranial aneurysm risk factor genes: relationship with intracranial aneurysm risk in a Chinese Han population

et al. 2015

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ABSTRACT. Few studies have examined the genes related to risk factors that may contribute to intracranial aneurysms (IAs). This study in Chinese patients aimed to explore the relationship between IA and 28 gene loci, proven to be associated with risk factors for IA. We recruited 119 patients with aneurysms and 257 controls. Single factor and logistic regression models were used to analyze the association of IA and IA rupture with risk factors. Twenty-eight single nucleotide polymorphisms (SNPs) in 22 genes were genotyped for the patient and control groups. SNP genotypes and allele frequencies were analyzed by the chi-square test. Logistic regression analysis identified hypertension as a factor that increased IA risk (P = 1.0 x 10 -4 ; OR, 2.500; 95%CI, 1.573-3.972); IA was associated with two SNPs in the TSLC2A9 gene: rs7660895 (P = 0.007; OR, 1.541; 95%CI, 1.126-2.110); and in the TOX gene: rs11777927 (P = 0.013; OR, 1.511; 95%CI, 1.088-2.098). Subsequent removal of the influence of family relationship identified between 12 of 119 patients enhanced the significant association of these SNPs with IA (P = 0.001; OR, 1.691; 95%CI, 1.226-2.332; and P = 0.006; OR, 1.587; 95%CI, 1.137-2.213 for rs7660895 and rs11777927, respectively). Furthermore, the minor allele of rs7660895 (A) was also associated with IA rupture (P = 0.007; OR, 2.196; 95%CI,. Therefore, hypertension is an independent risk factor for IA. Importantly, the TSL-C2A9 (rs7660895) and TOX (rs11777927) gene polymorphisms may be associated with formation of IAs, and rs7660895 may be associated with IA rupture.

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“…Abnormal TG metabolism can lead to other disease phenotypes such as obesity, hepatic steatosis and hepatic insulin resistance, all conditions that are exacerbated by continued TG accumulation (5). It is known that common genetic variants in candidate metabolic genes contribute to the expression of diseases such as MetS (6)(7)(8). Similarly, genetic determinants of TG metabolism may contribute to the dysregulation of energy homeostasis and thus other common CVDassociated phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Rare ATGL haplotypes are associated with increased plasma triglyceride concentrations in the Greenland Inuit

Johansen¹,

Gallinger²,

Wang³

et al. 2010

International Journal of Circumpolar Health

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Objectives. To genotype common genetic variants found in the adipose triglyceride lipase (ATGL) gene and test them for association with cardiovascular disease risk factors in the Greenland Inuit. Study design. Candidate gene association study of discrete and quantitative traits related to cardiovascular health. Methods. ATGL was sequenced in 0 European subjects to identify DNA sequence variants. The identified polymorphisms were subsequently genotyped in a population-based cohort of 1,218 unrelated Greenland Inuit subjects, ascertained from the Greenland Population Study. Genotypes and reconstructed haplotypes were tested for association with cardiovascular disease risk factors using additive, dominant or recessive models, corrected for age, sex and body mass index. Results. Five single nucleotide polymorphisms and one 4-base pair deletion were identified in the European sample and were similarly polymorphic in the Greenland Inuit. Independently, variants were not associated with any cardiovascular traits. However, reconstructed rare ATGL haplotypes were associated with increased plasma triglyceride (TG) concentrations compared to the major haplotype under a dominant model (.±0.7 mmol/L and .±0.6 mmol/L, respectively, p=0.006). Conclusions. Rare ATGL haplotypes are associated with increased plasma TG concentrations in the Greenland Inuit.

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Association between the FTO rs9939609 polymorphism and the metabolic syndrome in a non-Caucasian multi-ethnic sample

Cited by 89 publications

References 14 publications

Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression

Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression

Intracranial aneurysm risk factor genes: relationship with intracranial aneurysm risk in a Chinese Han population

Rare ATGL haplotypes are associated with increased plasma triglyceride concentrations in the Greenland Inuit

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