Investigation of Fc gamma RIIA and Fc gamma RIIIA polymorphism in multiple sclerosis: a case control study

ABSTRACT

Multiple Sclerosis [MS], the most common demyelinating disease of the CNS, is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of IgG [Fc gamma R] might induce inflammatory responses through linking the humoral and cellular immune responses by targeting immune complexes to effector cells. Polymorphisms in some Fc gamma R genes are associated with various infectious and autoimmune diseases, probably due to their effects on different binding capacities of encoded receptors for IgG containing immune complexes. To investigate the importance of Fc gamma R polymorphisms in susceptibility to MS. One hundred and fifty MS patients and 136 age and sex matched controls were genotyped for Fc gamma RIIA and Fc gamma RIIIA gene polymorphisms using PCR-RFLP method. The allelic and genotypic frequencies of the Fc gamma RIIA and Fc gamma RIIIA did not differ significantly between the MS patients and controls. There was no association between allelic polymorphism of Fc gamma RIIIA and severity of disease based on Expanded Disability Status Scale [EDSS] score. However, significant association between inherited Fc gamma RIIA genotype and disease activity [p=0.001] or progression index was revealed [p=0.014]. EDSS values showed that Fc gamma RIIA [H/H] and [H/R] genotypes were associated with a lower EDSS score in relapsing-remitting MS and in the total MS population [P=0.001] but not [R/R] genotype. Considering the detrimental role of autoantibodies in the pathogenesis of MS, our results suggest that the inherited Fc gamma RIIA alleles could affect the severity of MS by influencing the clearance rate of immune complexes and autoantibodies. The results of the present study add the Fc gamma RIIA gene to the gene networks which determine the severity of MS in southern Iran