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Association of the tumour necrosis factor α −308G/A polymorphism with the risk of diabetes in an elderly population-based cohort

Genes & Immunity volume 3, pages 225–228 (2002)Cite this article

Abstract

Ample evidence supports a role for tumour necrosis factor α (TNFα) in the development of type 2 diabetes and cardiovascular disease. TNFα expression was found to be influenced by a −308G/A polymorphism in the promoter of the gene encoding TNFα (TNF). We investigated the contribution of this polymorphism to diabetes and cardiovascular mortality in a population-based cohort of 664 subjects aged 85 years and over (Leiden 85-plus Study). The −308G/A TNF promoter polymorphism was associated with the prevalence of diabetes in old age (P = 0.006). The risk of diabetes among subjects homozygous for the A-allele was estimated to be 4.6-fold (95% CI, 1.6–13.3) higher than among subjects homozygous for the common G-allele. The promoter polymorphism did not, however, predict mortality from all causes, cardiovascular diseases, cancer or infectious diseases during a 10-year follow-up period. In addition to the promoter polymorphism, TNFa and TNFc microsatellite genotypes were determined but these polymorphisms were not associated with morbidity or mortality. In conclusion, the −308G/A polymorphism in the TNF promoter is strongly associated with the risk of diabetes but not cardiovascular mortality in old age.

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Acknowledgements

We wish to thank the Central Bureau of Statistics for generously making available the mortality statistics and database linking.

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Authors and Affiliations

  1. Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands

    B T Heijmans, S Droog, C Kluft, D L Knook & P E Slagboom

  2. Department of General Internal Medicine, Gerontology and Geriatrics Section, Leiden University Medical Centre, Leiden, The Netherlands

    B T Heijmans, R G J Westendorp & D L Knook

  3. Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands

    R G J Westendorp

  4. BTH and PES: Molecular Epidemiology Section, Dept. Medical Statistics, Leiden University Medical Centre, Leiden, The Netherlands

    B T Heijmans & P E Slagboom

Authors
  1. B T Heijmans
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  2. R G J Westendorp
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  3. S Droog
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  4. C Kluft
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  5. D L Knook
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  6. P E Slagboom
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Correspondence to B T Heijmans.

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This study was supported by grant no. 94.047 from The Netherlands Heart Foundation.

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Heijmans, B., Westendorp, R., Droog, S. et al. Association of the tumour necrosis factor α −308G/A polymorphism with the risk of diabetes in an elderly population-based cohort. Genes Immun 3, 225–228 (2002). https://doi.org/10.1038/sj.gene.6363859

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  • DOI: https://doi.org/10.1038/sj.gene.6363859

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