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No evidence of a functionally significant polymorphism of the BCL2 gene in Danish, Finnish and Basque type 1 diabetes families

Genes & Immunity volume 2, pages 398–400 (2001)Cite this article

Abstract

Accumulating evidence has suggested a role for the anti-apoptotic protein BCL2 in the development of autoimmune diseases, including type 1 diabetes mellitus (T1DM). Recently, the first BCL2 polymorphism (Ala43Thr) with association to T1DM in a Japanese population was reported. The polymorphism was found significantly more frequent in control individuals (14.5%) than in T1DM patients (6.8%), and was furthermore found to be functionally relevant, promoting a increased sensitivity to apoptosis when overexpressed in an IL-7 dependent mouse pre-B cell line. To investigate the relevance of the polymorphism in Caucasians, we have genotyped nearly 1400 individuals comprising Danish, Finnish and Basque T1DM family materials, using a PCR-based RFLP assay. In contrast to what was observed in Japanese diabetic/control individuals, we find no evidence for association of the BCL2 Ala43Thr polymorphism to T1DM in Danish, Finnish and Basque Type 1 diabetes families.

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References

  1. Nerup J, Mandrup-Poulsen T, Helqvist S et al One the pathogenesis of IDDM Diabetologia 1994 37 (Suppl 2) 82–89

    Article  Google Scholar 

  2. Mauricio D, Mandrup-Poulsen T Apoptosis and pathogenesis of IDDM. A question of life and death Diabetes 1998 47 1537–1543

    Article  CAS  Google Scholar 

  3. Kroemer G The proto-oncogene Bcl-2 and its role in regulating apoptosis Nat Med 1997 3 614–620

    Article  CAS  Google Scholar 

  4. Theofilopoulos AN, Kono DH The genes of systemic autoimmunity Proc Assoc Am Physicians 1999 111 228–240

    Article  CAS  Google Scholar 

  5. Mountz JD, Wu J, Cheng J et al Autoimmune disease. A problem of defective apoptosis Arthritis Rheum 1994 37 1415–1420

    Article  CAS  Google Scholar 

  6. Komaki S, Kohno M, Matsuura N The polymorphic 43Thr bcl-2 protein confers relative resistance to autoimmunity: an analytical evaluation Hum Genet 1998 103 435–440

    Article  CAS  Google Scholar 

  7. Larsen ZM, Kristensen OP, Mato E et al IDDM12 (CTLA4) on 2q33 and IDDM13 on 2Q34 in genetic susceptibility to type 1diabetes (insulin dependent) Autoimmunity 1999 31 35–42

    Article  CAS  Google Scholar 

  8. Pociot F, Veijola R, Johannesen J et al Analysis of a interferon-γ gene (IFNG) polymorphism in Danish and Finnish insulin-dependent diabtes mellitus (IDDM) patients and controlsubjects J Interferon Cytokine Res 1997 17 87–93

    Article  CAS  Google Scholar 

  9. Nanclares GP, Bilbao JR, Nistico R et al No evidence of association of chromosome 2q with Type 1 diabetes in the Basque population Diabetologia 1999 42 119–120

    Article  Google Scholar 

  10. Risch NJ Searching for genetic determinants in the new millennium Nature 2000 405 847–856

    CAS  PubMed  Google Scholar 

  11. Johansson C, Castillejo-Lopez C, Johanneson B et al Association analysis with microsatellite and SNP markers does not support the involvement of BCL-2 in systemic lupus erythematosus in Mexican and Swedish patients and their families Genes Immun 2000 1 380–385

    Article  CAS  Google Scholar 

  12. Merriman T, Twells R, Merriman M et al Evidence by allelic association-dependent methods for a type 1 diabetes polygene (IDDM6) to chromosome 18q21 Hum Mol Genet 1997 6 1003–1010

    Article  CAS  Google Scholar 

  13. Kristiansen OP, Larsen ZM, Pociot F CTLA-4 in autoimmune diseases – a general susceptibility gene to autoimmunity? Genes Immun 2000 1 170–184

    Article  CAS  Google Scholar 

  14. Merriman TA, Heather JC, Iain AE et al Suggestive evidence for association of human chromosome 18q12-q21 and its orthologue on rat and mouse chromosome 18 with several autoimmune diseases Diabetes 2001 50 184–194

    Article  CAS  Google Scholar 

  15. Gatenby PA, Irvine M The bcl-2 proto-oncogene is overexpressed in systemic lupus erythematosus J Autoimmun 1994 7 623–631

    Article  CAS  Google Scholar 

  16. Mehrian R, Quismorio FP, Strassmann G Synergistic effect between IL-10 and bcl-2 genotypes in determining susceptibility to systemic lupus erythematosus Arthritis Rheum 1998 41 596–602

    Article  CAS  Google Scholar 

  17. Iwahashi H, Hanafusa T, Eguchi Y Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: inhibition by Bcl-2 Diabetologia 1996 39 530–536

    Article  CAS  Google Scholar 

  18. Rabinovitch A, Suarez-Pinzon W, Strynadka K Transfection of human pancreatic islets with an anti-apoptotic gene (bcl-2) protects β-cells from cytokine-induced destruction Diabetes 1999 48 1223–1229

    Article  CAS  Google Scholar 

  19. Bergholdt R, Larsen ZM, Andersen NA et al Characterization of new polymorphisms in the 5′UTR of the human interleukin-1 receptor type 1 (IL1R1) gene: linkage to type 1 diabetes and correlation to IL-1R1 plasma level Genes Immun 2000 1 495–500

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Drs J Johannesen and OP Kristensen, the DSGD, and the DIEGG for collecting part of the Danish families used in this study, and furthermore Dr Luis Castaño for generously providing the Basque material.

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Authors and Affiliations

  1. Steno Diabetes Center, Niels Steensensvej 2, Gentofte, 2820, Denmark

    PE Heding, AE Karlsen, J Nerup & F Pociot

  2. Department of Paediatrics, Kajaanintie 50, Oulu, 90220, Finland

    R Veijola

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  1. PE Heding
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  2. AE Karlsen
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  3. R Veijola
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  4. J Nerup
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  5. F Pociot
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Correspondence to F Pociot.

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Heding, P., Karlsen, A., Veijola, R. et al. No evidence of a functionally significant polymorphism of the BCL2 gene in Danish, Finnish and Basque type 1 diabetes families. Genes Immun 2, 398–400 (2001). https://doi.org/10.1038/sj.gene.6363788

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  • DOI: https://doi.org/10.1038/sj.gene.6363788

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