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Gene polymorphisms of arylsulfatase A in relapse remitting multiple sclerosis : genotype-phenotype correlation and estimation of disease progression using multiple sclerosis severity score

Arylsulfatase A (ASA) is lysosomal enzyme involved in catabolism of cerebroside-sulfate, major lipid constituent of oligodendrocyte membranes. Various polymorphisms in ASA gene have been described, leading to different levels of enzyme deficiency. Progressive demyelination occurs in metachromatic leukodystrophy (MLD), while the condition of ASA-pseudodeficiency (ASA-PD) is suggested to contribute to complex pathogenesis of multiple sclerosis (MS). Genotype-phenotype correlation is thus useful in estimation of disease severity and progression, and may be analyzed using recently introduced Multiple Sclerosis Severity Score (MSSS) method. We have analyzed the frequency of two most common mutations associated with ASA-PD in 56 patients with diagnosis of relapse-remitting multiple sclerosis. The presence of mutations was determined by polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). To determine whether there is a difference between disability level and/or disease progression in patients with or without mutations we have estimated disability level using Expanded disability status scale (EDSS) and disease progression using Multiple Sclerosis Severity Score for all patients. Correlation of genotypes and disease progression was analyzed by Kruskal-Wallis test (MSSS test, computer programme, version 3.0). The presence of either one or both mutations was determined in 13 patients (both mutations in 8 patients, only N350S mutation in 4 patients, while 1 patient carried only 1524+95 A-G mutation). Nine of the mutations carriers had mild disability (EDSS=0-4.0), 1 had moderate disability (EDSS=4.5-5.5), and 3 had severe disability (EDSS=6.0-10.0). Although we found no statistically significant correlation of genotypes and MSSS in the group of 56 MS patients, we have observed that only 3 MS patients who were mutation carriers showed MSSS values lower than 5.000 while in other MS patients-mutation carriers the MSSS value ranged from 5.267 to 9.453. Since MSSS method takes into account disability as well as the duration of the disease it is more appropriate indicator of disease progression than EDSS which presents only the disability level. MSSS is a powerful method for comparing disease progression in different groups of patients and is proven to be useful for identifying factors that may influence disease progression such as the presence of gene polymorphisms.

multiple sclerosis severity score; gene polymorphisms; arylsulfatase A

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