5′ Flanking Variants of Resistin Are Associated With Obesity

Engert, James C.; Vohl, Marie‐Claude; Williams, Scott M.; Lepage, Pierre; Loredo-Osti, J. Concepción; Faith, Janet; Doré, Carole; Renaud, Yannick; Burtt, Noél P.; Villeneuve, Amélie; Hirschhorn, Joel N.; Altshuler, David; Groop, Leif; Després, Jean‐Pierre; Gaudet, Daniel; Hudson, Thomas J.

doi:10.2337/diabetes.51.5.1629

Cited by 158 publications

(150 citation statements)

References 26 publications

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“…Several polymorphisms have been found in the promoter region of the resistin gene and it has been reported that one polymorphism, −420 C>G, was related to plasma resistin levels and diabetes [20,21,30]. In this study, we investigated the molecular mechanism underlying the effect of the −420G/C variation on the expression of the resistin gene.…”

Section: Discussionmentioning

confidence: 98%

Regulation of human resistin gene expression in cell systems: an important role of stimulatory protein 1 interaction with a common promoter polymorphic site

et al. 2005

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Aims/hypothesis: Resistin is an adipokine that might link obesity and insulin resistance. A common polymorphism of the human resistin gene, −420C>G, is a major determinant of plasma resistin concentrations as well as resistin mRNA expression in human adipose tissue. In this study, we investigated the regulatory mechanism by which this polymorphism affects resistin expression. Methods: Electrophoretic mobility shift assay was performed to identify the transcription factors binding to the −420G region. Transient transfection and reporter assay were used to measure promoter activities of the resistin gene. The binding ability of stimulatory protein 1 (Sp1) in response to adipocyte differentiation or high glucose concentrations was also measured. Results: Sp1 and stimulatory protein 3 (Sp3) specifically bound to the region around −420G of the human resistin gene. Overexpression of Sp1 increased the promoter activity regardless of −420 genotypes, while the promoter activity of the −420G construct was two-fold higher than that of the −420C construct. In contrast, overexpression of Sp3 scarcely increased the promoter activity. The binding ability of Sp1 to the −420G region was increased in response to adipocyte differentiation. Mithramycin A, an inhibitor of DNA binding of Sp1, reduced the effect of high glucose on transcription induction of the resistin gene in adipocytes. Conclusions/interpretation: These results suggest that Sp1 is an important factor regulating transcription of human resistin gene. A common polymorphism of the human resistin promoter, −420C>G, is critical for the binding of Sp1 and modulates the transcriptional activity of the resistin gene by changing the binding ability of Sp1. In addition, Sp1 may be involved in the increase of resistin expression by hyperglycaemia.

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Section: Discussionmentioning

confidence: 98%

Regulation of human resistin gene expression in cell systems: an important role of stimulatory protein 1 interaction with a common promoter polymorphic site

et al. 2005

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“…A previous study identified a single nucleotide polymorphism in the RETN gene associated with resistin mRNA expression levels in human adipose tissue (Smith et al, 2003). Genetic variation in the RETN has been found in association with obesity (Engert et al, 2002) and type 2 diabetes (Ma et al, 2002;Wang et al, 2002). Obesity and diabetes related phenotypes, such as sum of skinfolds, leptin levels and percentage body fat, have been linked to this region on chromosome 19 (Chagnon et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Cross-species replication of a resistin mRNA QTL, but not QTLs for circulating levels of resistin, in human and baboon

et al. 2008

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“…183 One resistin 5 0 -flanking polymorphism, À420C4G, has been analysed for association with obesity with conflicting results. 184,185 The À420C4G G/G genotype displays significantly increased basal promoter activity in adipocytes, and is associated with significantly higher resistin mRNA levels in human abdominal subcutaneous fat. 186 Furthermore, an ATG repeat in the 3 0 -UTR region of resistin has been associated with insulin resistance, but not with obesity.…”

Section: Pathways Controlling Lipid Storage In Adipocytesmentioning

confidence: 99%

Obesity and polymorphisms in genes regulating human adipose tissue

Dahlman

Arner

2007

Int J Obes

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Obesity is the result of an imbalance between food intake and energy expenditure resulting in the storing of energy as fat. Adipose tissue contains the largest store of energy in the body and plays important roles in regulating energy partitioning. Developments in genomics, in particular microarray-based expression profiling, have provided scientists with a number of new candidate genes whose expression in adipose tissue is regulated by obesity. Integrating expression profiles with genome-wide linkage and/or association analyses is a promising strategy to identify new genes underlying susceptibility to obesity. This article provides a comprehensive review of adipose-tissue-expressed genes implicated in predisposition to human obesity. The authors consider the following genes of particular interest: peroxisome proliferator-activated receptor gamma and, potentially, INSIG2 acting in adipogenesis; the adrenoreceptors beta 2 and 3, as well as hormone-sensitive lipase acting on lipolysis; uncoupling protein 2 acting in mitochondria energy expenditure; and among secreted molecules the cytokine tumor necrosis factor alpha and the hormone leptin. With the rapid development in genome research, we predict that additional alleles in genes regulating adipose tissue function will be established as risk factors for common obesity in the coming years. This has important implications for the prevention of obesity and may also offer new therapeutic targets.

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5′ Flanking Variants of Resistin Are Associated With Obesity

Abstract: In contrast, in case/control and family-based study populations from Scandinavia, we saw no effect on BMI with either of these promoter variants. No association was seen with diabetes in any of the population samples.

Cited by 158 publications

References 26 publications

Regulation of human resistin gene expression in cell systems: an important role of stimulatory protein 1 interaction with a common promoter polymorphic site

Regulation of human resistin gene expression in cell systems: an important role of stimulatory protein 1 interaction with a common promoter polymorphic site

Cross-species replication of a resistin mRNA QTL, but not QTLs for circulating levels of resistin, in human and baboon

Obesity and polymorphisms in genes regulating human adipose tissue

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