You are here

Article Text

Article menu
Download PDFPDF
Electronic letters
Genetic and functional evaluation of an interleukin-12 polymorphism (IDDM18) in families with type 1 diabetes
  1. R Bergholdt1,
  2. P Ghandil2,
  3. J Johannesen1,
  4. O P Kristiansen1,
  5. I Kockum3,
  6. H Luthman4,
  7. K S Rønningen5,
  8. J Nerup1,
  9. C Julier2,
  10. F Pociot1
  1. 1Steno Diabetes Centre, Gentofte, Denmark
  2. 2Institut Pasteur, Paris, France
  3. 3Karolinska Institutet, Stockholm, Sweden
  4. 4Lund University, Sweden
  5. 5Norwegian Institute of Public Health, Oslo, Norway
  1. Correspondence to:
 Dr F Pociot
 Flemming Pociot, Steno Diabetes Centre, 2 Niels Steensensvej, DK-2820 Gentofte, Denmark; fpocsteno.dk

https://doi.org/10.1136/jmg.2003.010454

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Type 1 (insulin dependent) diabetes mellitus (T1DM) [MIM 222100] is an autoimmune disease with both genetic and environmental components. The HLA region is the major genetic susceptibility region, but in addition several minor susceptibility loci have been suggested. Their identification is, however, difficult because of the complexity of the disease.1

    Recently, a new susceptibility locus, IDDM18 [MIM 605598], was reported and mapped to chromosome 5q31.1-q33.1, close to the IL12B gene, which encodes the p40 subunit of interleukin (IL) 12.2–4 IL-12p40 production influences T cell response, and may therefore be important in T1DM pathogenesis.5 IL-12 drives the differentiation of T lymphocytes towards the Th1 subset, characterised by production of cytokines leading to cell mediated immunity.6–8 Furthermore, in the non-obese diabetic (NOD) mouse, IL-12 has been shown to play a primary role in T1DM induction.5,9,10 In addition, IL-12 is important in immune reactivity against infections, but it has been shown that in the absence of infection, IL-12 induced autoreactive T cell responses might predispose to self destructive immunity.11,12 IL-12 is a disulphide linked heterodimer composed of a heavy chain of 40 kDa, p40, and a light chain of 35 kDa, p35, encoded by two separate genes.2,13 The gene for the p35 subunit, IL12A, is located on chromosome 3p12-q13.2. The two subunits of IL-12 are in contrast to most cytokines, which possess only one polypeptide chain. Many cell types express the p35 chain, while the p40 subunit is expressed principally by activated macrophages and B cells.2 The heterodimer, p70 or p75, is the biologically active IL-12.13

    IL12B is a candidate for IDDM18, as linkage disequilibrium is confined to a 30 kb region on chromosome 5, in which IL12B is the only known gene.4 Several polymorphisms …

    View Full Text