Abstract
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 language | English |
---|---|
Journal | Immunogenetics |
Volume | 52 |
Issue number | 1-2 |
Pages (from-to) | 107-111 |
Number of pages | 5 |
DOIs | |
Publication status | Published - 2000 |
Externally published | Yes |
Keywords
- 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