Linkage between obesity and a marker near the tumor necrosis factor-alpha locus in Pima Indians.

Norman, R. A.; Bogardus, Clifton; Ravussin, Éric

doi:10.1172/jci118016

Cited by 127 publications

(70 citation statements)

References 32 publications

(17 reference statements)

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“…A potential role for the TNF-a locus in obesity is also supported by a linkage study, which reported a relationship between the TNF-a locus and various global measures of adiposity in Pima Indians and European Caucasians. 12,20 Thus, our data support the hypothesis that a genetic variant of the TNF-a gene may contribute to the development of obesity.…”

Section: Discussionsupporting

confidence: 84%

Tumor necrosis factor-α−308 G/A polymorphism in obese Caucasians

et al. 2001

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OBJECTIVE: Tumor necrosis factor-a (TNF-a) is expressed primarily in adipocytes, and elevated levels of this cytokine have been linked to obesity and insulin resistance. Recently, the A allele of a polymorphism in the 5H -¯anking region of the TNF-a gene (G7308A) has been reported to be more frequent in obese than in lean subjects and has also been associated with increased expression of this cytokine in fat tissue and in¯uences fat mass and insulin resistance. We, therefore, examined the relationship between this variant and obesity in a German Caucasian population. SUBJECTS AND METHODS:We genotyped 176 index subjects recruited within the framework of the BErG (Berlin Erna Èhrung Geschwister)-Study for the TNF-a-G7308A polymorphism. Subjects were characterized for weight, height, waist and hip circumference, body mass index (BMI), body composition, glucose tolerance, leptin and angiotensinogen levels. RESULTS: The frequency of the 7308A allele (0.18) was similar to that reported previously and genotype distribution was in Hardy ± Weinberg equilibrium (GG, n 118; GA, n 53; AA, n 5). There was a signi®cant difference in allele frequencies of the polymorphism by BMI quartiles (I,`27.3 kgam 2 ; II, 27.3 ± 31.9 kgam 2 ; III, 31.9 ± 36.5 kgam 2 ; IV, b 36.5 kgam 2 , in each quartile n 44) with 7308A allele carriers having a higher BMI than G allele carriers (P 0.013). Despite previous smaller studies that have related insulin resistance to the G7308A polymorphism, we found no relationship between glucose and insulin response during an oral glucose tolerance test (OGTT) and the polymorphism. Furthermore, none of the plasma parameters were related to the polymorphism. CONCLUSION: Our ®ndings support the hypothesis that the G7308A polymophism of the TNF-a gene is associated with BMI. The G7308A polymorphism may, therefore, represent a genetic marker for increased susceptibility for obesity in Caucasians.

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Section: Discussionsupporting

confidence: 84%

Tumor necrosis factor-α−308 G/A polymorphism in obese Caucasians

et al. 2001

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“…15 The TNFA locus has been linked to obesity. 170 One TNFA promoter SNP at position À308 that influences gene transcription has in a recent metaanalysis been associated with a modest increased risk of developing obesity, OR 1.23. 171,172 The C allele of one polymorphism in the IL6 promoter, ÀG174C, has in different populations been associated with obesity and decreased risk of T2DM.…”

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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“…31 A polymorphism near the transcription start site of TNFa (G to A at position À308) has been associated with obesity in several populations. 32,33 It was recently found that the latter polymorphism only in¯uences body fat content in its homozygous form 34 in turn, suggesting that TNFa is a recessive obesity gene.…”

Section: Tumor Necrosis Factor Alpha (Tnfa)mentioning

confidence: 99%

Hunting for human obesity genes? Look in the adipose tissue!

Arner

2000

Int J Obes

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Linkage between obesity and a marker near the tumor necrosis factor-alpha locus in Pima Indians.

Cited by 127 publications

References 32 publications

Tumor necrosis factor-α−308 G/A polymorphism in obese Caucasians

Tumor necrosis factor-α−308 G/A polymorphism in obese Caucasians

Obesity and polymorphisms in genes regulating human adipose tissue

Hunting for human obesity genes? Look in the adipose tissue!

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