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

International Journal of Obesity volume 25, pages 581–585 (2001)Cite this article

Abstract

OBJECTIVE: Tumor necrosis factor-α (TNF-α) 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 5′-flanking region of the TNF-α gene (G−308A) 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 influences 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 Ernährung Geschwister)- Study for the TNF-α-G−308A 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 −308A 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 significant difference in allele frequencies of the polymorphism by BMI quartiles (I,<27.3 kg/m2; II, 27.3–31.9 kg/m2; III, 31.9–36.5 kg/m2; IV,>36.5 kg/m2, in each quartile n=44) with −308A allele carriers having a higher BMI than G allele carriers (P=0.013). Despite previous smaller studies that have related insulin resistance to the G−308A 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 findings support the hypothesis that the G−308A polymophism of the TNF-α gene is associated with BMI. The G−308A polymorphism may, therefore, represent a genetic marker for increased susceptibility for obesity in Caucasians.

International Journal of Obesity (2001) 25, 581–585

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Acknowledgements

We would like to thank Monika Hantschke-Brüggemann, Brigitte Egbers, Brigitte Geue and Klaus Schlotter for expert technical assistance in analyzing the plasma samples. This study was supported by a research grant from the Bundesministerium für Bilding und Forschung (BMBF 685.20) and from the Universitätsklinikum Benjamin Franklin, Berlin (FSP-EB 1999/2000).

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Endocrinology and Nephrology, Universitätsklinkum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany

    E Brand, U Schorr, I Kunz, E Kertmen, J Ringel, A Distler & AM Sharma

  2. Division of Biochemistry and Physiology of Nutrition, German Institute of Human Nutrition, Potsdam-Rehbrücke, Potsdam, Germany

    I Kunz

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  1. E Brand
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  2. U Schorr
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Correspondence to AM Sharma.

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Brand, E., Schorr, U., Kunz, I. et al. Tumor necrosis factor-α−308 G/A polymorphism in obese Caucasians. Int J Obes 25, 581–585 (2001). https://doi.org/10.1038/sj.ijo.0801576

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