Implication of platelet-activating factor receptor A224D mutation in susceptibility to relapsing-remitting multiple sclerosis: A Tunisian population study

• Published in: Pathologie biologie (Paris) 2012-06, Vol.60 (3), p.185-189
• Main Authors: Messadi, A, Fekih-Mrissa, N, Zaouali, J, Layouni, S, Nsiri, B, Yedeas, M, Raies, A, Mrissa, R, Gritli, N
• Format: Article
• Language: fre
• Subjects: Adult; Alanine - genetics; Amino Acid Substitution - genetics; Aspartic Acid - genetics; Disease Progression; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetics, Population; Humans; Male; Multiple Sclerosis, Relapsing-Remitting - diagnosis; Multiple Sclerosis, Relapsing-Remitting - epidemiology; Multiple Sclerosis, Relapsing-Remitting - genetics; Mutation, Missense - physiology; Platelet Membrane Glycoproteins - genetics; Receptors, G-Protein-Coupled - genetics; Severity of Illness Index; Tunisia - epidemiology; Young Adult
• ISSN: 1768-3114
• DOI: 10.1016/j.patbio.2011.04.004

Platelet-activating factor interacts with its specific receptor and mediates leucocytes transmigration into central nervous system and expression of HLA molecules on antigens-presenting cells. These features are the major characteristics of multiple sclerosis pathology. In the present study, we investigated the role of platelet-activating factor receptor A224 mutation in the susceptibility to relapsing-remitting form of MS in a Tunisian population. Forty-seven multiple sclerosis patients and 72 healthy controls were genotyped for platelet-activating factor receptor A224D mutation using polymerase chain reaction-restriction fragment length polymorphism technique. We used three models of inheritance: the codominant, dominant and recessive models. Our results showed a predisposing effect of platelet-activating factor receptor 224D variant on susceptibility to relapsing-remitting multiple sclerosis (30% vs 48.1%, OR [IC 95%]=2.04 [1.04-3.99], P=0.023). Our results were also consistent with a dominant model of inheritance when comparing mild genotype (AA) with carriers of one or two copies of mutant allele (AD+DD) (55.7% vs 31.9%, OR [IC 95%]=2.92 [1.34-6.81], P=0.006). No effect of this mutation was shown when considering the age at disease onset, disease severity or gender. This first study reports an implication of platelet-activating factor receptor A224D mutation in the susceptibility to relapsing-remitting multiple sclerosis in Tunisian population. Further studies will be necessary to confirm the dominant role of PAFR A224D mutation and to elucidate the effect of this mutation on platelet-activating factor/platelet-activating factor receptor pathways.