The intercellular adhesion molecule-1 K469E polymorphism in type 1 diabetes

Ole P. Kristiansen, Runa L. Nolsøe, Heidi Holst, Sine Reker Hadrup, Zenia M. Larsen, Jesper Johannesen, Jørn Nerup, Flemming Pociot, Thomas Mandrup-Poulsen

Research output: Contribution to journalJournal articleResearchpeer-review


Type 1 (insulin-dependent) diabetes is a complex trait. The region harboring the ICAM1 gene on 19p13 links to type 1 diabetes, and a growing body of evidence indicates that intercellular adhesion molecule-1 (ICAM-1) could play a role in type 1 diabetes development. Recently, association studies of an ICAM-1 K469E polymorphism in type 1 diabetes populations have reported conflicting results. Hence, we performed a transmission disequilibrium test analysis of the ICAM-1 K469E variations in 253 Danish type 1 diabetes families. Linkage and association was not found between the ICAM-1 K469E variation and type 1 diabetes in Danish patients (Ptdt ≥ 0.48), and our data did not indicate an interaction between ICAM1 and IDDM1 in predisposition to type 1 diabetes in Danes (P=0.78). We did not observe significant association with late-onset type 1 diabetes (Ptdt≥0.12) or differences in transmission patterns between groups of affected offspring stratified for age at onset (P≥0.19), as suggested in Japanese patients. Combined analysis of the present and previously reported transmission data comprising 728 affected offspring of Romanian, Finnish, and Danish ancestry suggested association between the ICAM-1 E469 allele and type 1 diabetes (Ptdt=0.013), but association was not found in the combined Scandinavian material. In conclusion, we found no association of the ICAM-1 K469E polymorphism with type 1 diabetes or its subsets stratified for age at onset and HLA risk in Danish patients. Analysis of ICAM-1 K469E transmissions reported in three populations suggested association to type 1 diabetes, but also demonstrated heterogeneity between populations.
Original languageEnglish
Issue number1-2
Pages (from-to)107-111
Number of pages5
Publication statusPublished - 2000
Externally publishedYes


  • Immunology
  • Genetics
  • Autoimmunity
  • ICAM1
  • IDDM
  • LFA-1
  • Transmission disequilibrium testing
  • HLA antigen
  • intercellular adhesion molecule 1
  • lymphocyte function associated antigen 1
  • article
  • DNA polymorphism
  • genetic linkage
  • genetic predisposition
  • heterozygosity
  • human
  • insulin dependent diabetes mellitus
  • Japan
  • major clinical study
  • onset age
  • priority journal
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • Denmark
  • Diabetes Mellitus, Type 1
  • Europe
  • Female
  • Humans
  • Infant
  • Intercellular Adhesion Molecule-1
  • Male
  • Middle Aged
  • Point Mutation
  • Polymorphism, Genetic


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