ABSTRACT
Previous studies suggested that increased activity of haem oxygenase 1 may ameliorate autoimmune neuroinflammation in experimental models of multiple sclerosis. This increased activity is associated with an augmented number of GT repeats (≥ 25) within the HMOX1 gene promoter. Here we examined 338 patients with multiple sclerosis to determine the influence of their HMOX1 gene promoter (GT)n polymorphism and other individual characteristics on the course of the disease. The patients were divided into those with "rapid" or "delayed" course, based on reaching expanded disability status scale step 4 within nine years of disease onset, and the correlations between the disease course and the investigated characteristics were sought using logistic regression analysis. No statistically significant effect of HMOX1 gene promoter (GT)n polymorphism on the rate of disability progression was found (P = 0.9). This was confirmed by Cox regression analysis, which did not find any difference in the cumulative risk of reaching expanded disability status scale step 4 between the patients with long and short HMOX1 gene promoter (P = 0.7). In contrast, covariates significantly associated with the faster disability progression were: progressive course of multiple sclerosis, shorter duration of disease-modifying treatment and older age at disease onset (P ≤ 0.04). The observed absence of effect of the HMOX1 promoter (GT)n polymorphism could be attributed to its known dualistic role in the pathogenesis of autoimmune disorders. As a secondary outcome, we have seen that disease-modifying drugs have the potential to delay disability progression in patients with multiple sclerosis.
