Intercellular adhesion molecule-1 K469E polymorphism: study of association with multiple sclerosis
Sergey Nejentsev1, Mikko Laaksonen, Pentti J Tienari
1Department of Virology, University of Turku, Finland. serneje@gene.cimr.cam.ac.uk
Abstract:
Intercellular adhesion molecule-1 (ICAM-1) is involved in the pathogenesis of multiple sclerosis (MS), whereas sequence variations in the ICAM-1 gene could potentially be responsible for the genetic susceptibility to MS. We studied an association of MS with the 13,848A>G (K469E) polymorphism of the ICAM-1 gene in Finnish and Spanish cases and controls and affected families. An increased risk for the AA (Lys(469)/Lys(469)) genotype was found in both populations. The effect observed was found to be strongest among the HLA-DQB1*0602-positive subjects, which implies genetic heterogeneity of MS. Meta-analysis of all published datasets supports increased risk of MS for the ICAM-1 Lys(469) homozygotes (relative risk = 1.3, p = 0.002).
Insights
Genetic variations in the Intercellular Adhesion Molecule-1 (ICAM-1) gene are linked to multiple sclerosis (MS) susceptibility. The ICAM-1 Lys469 homozygote genotype increases MS risk, particularly in HLA-DQB1*0602-positive individuals.
Area of Science:
- Genetics
- Immunology
- Neurology
Background:
- Intercellular Adhesion Molecule-1 (ICAM-1) plays a role in the pathogenesis of multiple sclerosis (MS).
- Genetic variations within the ICAM-1 gene may contribute to MS susceptibility.
- Previous studies suggest a potential link between ICAM-1 and MS, but further investigation is warranted.
Purpose of the Study:
- To investigate the association between the ICAM-1 13,848A>G (K469E) polymorphism and multiple sclerosis (MS) risk.
- To examine the influence of this polymorphism in Finnish and Spanish populations.
- To explore potential interactions with HLA-DQB1*0602 in MS genetic susceptibility.
Main Methods:
- Case-control study design involving Finnish and Spanish populations.
- Genotyping of the ICAM-1 13,848A>G (K469E) polymorphism.
- Analysis of affected families.
- Meta-analysis of published datasets.
Main Results:
- An increased risk for the AA (Lys(469)/Lys(469)) genotype of ICAM-1 was observed in both Finnish and Spanish MS cases compared to controls.
- This association was particularly pronounced in subjects positive for the HLA-DQB1*0602 allele.
- Meta-analysis of all available data confirmed a significant increased risk of MS for ICAM-1 Lys(469) homozygotes (RR = 1.3, p = 0.002).
Conclusions:
- The ICAM-1 Lys(469) homozygote genotype is associated with an increased risk of multiple sclerosis.
- Genetic heterogeneity in MS may be influenced by interactions between ICAM-1 variants and HLA-DQB1*0602.
- These findings contribute to understanding the genetic underpinnings of MS susceptibility.
