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Intercellular adhesion molecule-1 gene polymorphisms in isolated polymyalgia rheumatica
Mahsa M Amoli1, Emma Shelley, Derek L Mattey
1ARC Epidemiology Unit, Manchester University Medical School, United Kingdom.
Objective:
In untreated polymyalgia rheumatica (PMR), high levels of circulating soluble intercellular adhesion molecule-1 (ICAM-1) have been observed. To investigate the clinical implication of ICAM-1 polymorphisms in isolated PMR, we examined their potential influence in an unselected series of patients.
Methods:
We studied 72 patients with isolated PMR and 129 ethnically matched controls from Lugo, Spain. Patients and controls were genotyped for HLA-DRB1 and ICAM-1 polymorphism at codons 241 and 469 by molecular methods.
Results:
The distribution of alleles and genotypes for each ICAM-1 polymorphism did not show significant differences between patients with isolated PMR and controls. There were also no associations between ICAM-1 polymorphisms and relapses of the disease. The latter was primarily associated with carriage of an HLA-DRB1*0401 allele (OR 7.2, p = 0.01), although all relapsed patients with HLA-DRB1*0401 also carried the GG genotype of the ICAM-1 polymorphism at codon 241. The presence of both HLA-DRB1*0401 and the GG241 ICAM-1 genotype gave an OR of 15.2 (p = 0.005) after correction for age and sex.
Conclusion:
Although ICAM-1 polymorphisms alone do not appear to be associated with disease severity in isolated PMR, the presence of both HLA-DRB1*0401 and the ICAM-1 codon 241 GG homozygosity was significantly associated with increased risk of relapses in these patients.
Insights
Intercellular adhesion molecule-1 (ICAM-1) gene variations do not directly impact polymyalgia rheumatica (PMR) severity. However, a specific ICAM-1 genotype combined with HLA-DRB1*0401 significantly increases the risk of PMR relapses.
Area of Science:
- Immunogenetics
- Rheumatology
Background:
- High levels of soluble intercellular adhesion molecule-1 (ICAM-1) are observed in untreated polymyalgia rheumatica (PMR).
- The role of ICAM-1 genetic variations in isolated PMR has not been fully elucidated.
Purpose of the Study:
- To investigate the clinical implications of ICAM-1 polymorphisms in isolated PMR.
- To examine the association between ICAM-1 gene variations and disease relapses in PMR patients.
Main Methods:
- Genotyping of 72 isolated PMR patients and 129 controls for HLA-DRB1 and ICAM-1 polymorphisms (codons 241 and 469).
- Molecular methods were employed for genotyping.
Main Results:
- No significant differences in ICAM-1 allele or genotype distribution were found between PMR patients and controls.
- ICAM-1 polymorphisms were not associated with disease relapses independently.
- Relapses were primarily linked to the HLA-DRB1*0401 allele (OR 7.2).
- A combination of HLA-DRB1*0401 and ICAM-1 codon 241 GG genotype significantly increased relapse risk (OR 15.2).
Conclusions:
- ICAM-1 polymorphisms alone are not associated with disease severity in isolated PMR.
- The co-occurrence of HLA-DRB1*0401 and ICAM-1 codon 241 GG homozygosity is significantly associated with an increased risk of relapses in PMR patients.