Single nucleotide polymorphisms in multiple sclerosis: disease susceptibility and treatment response biomarkers
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IMMUNOLOGY IN SERBIA
Single nucleotide polymorphisms in multiple sclerosis: disease susceptibility and treatment response biomarkers Vera Pravica • Dusan Popadic • Emina Savic Milos Markovic • Jelena Drulovic • Marija Mostarica-Stojkovic
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Published online: 6 March 2012 Ó Springer Science+Business Media, LLC 2012
Vera Pravica
Abstract Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by unpredictable and variable clinical course. Etiology of MS involves both genetic and environmental factors. New technologies identified genetic polymorphisms associated with MS susceptibility among which immunologically relevant genes are significantly overrepresented. Although individual genes contribute only a small part to MS susceptibility, they might be used as biomarkers, thus helping to identify accurate diagnosis, predict clinical disease course and response to therapy. This review focuses on recent progress in research on MS genetics with special emphasis on the possibility to use single nucleotide polymorphism of candidate genes as biomarkers of susceptibility to disease and response to therapy. Keywords Multiple sclerosis Genetic polymorphism Biomarkers Interferon beta Pharmacogenomics Ethnic variations
Introduction Multiple sclerosis (MS), an acquired inflammatory and neurodegenerative, chronic disorder of the central nervous system (CNS), is the most frequent cause of severe nontraumatic neurological disability in young adults of European origin [1]. The prevalence rate of MS was reported to be about 80–100/100,000 and female-to-male ratio approximately 2 [1, 2]. It is an immune-mediated disease of unknown etiology. However, it is generally accepted that MS is a multifactorial disorder of the CNS that results from the interaction of both genetic and environmental factors.
V. Pravica (&) D. Popadic E. Savic M. Markovic M. Mostarica-Stojkovic Institute of Microbiology and Immunology, University of Belgrade School of Medicine, Dr Subotica 1, 11000 Belgrade, Serbia e-mail: [email protected] J. Drulovic Institute of Neurology CCS, University of Belgrade School of Medicine, Belgrade, Serbia
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Among many candidate genes, those coding the major histocompatibility complex (MHC) molecules exert the greatest individual effect on risk for the disease development [3]. On the other hand, recent epidemiological studies strongly suggest that certain environmental risk factors, such as ultraviolet radiation, vitamin D levels, smoking and infection with Epstein–Barr virus, also increase the risk for MS [4–7]. Cardinal features of MS pathology comprise inflammation, demyelination and axonal degeneration within CNS [2]. Immunopathological studies demonstrated that the mechanisms of myelin and oligodendrocyte damage differ between the patients, implicating inter-individual heterogeneity of MS lesions with four distinct patterns of demyelination [8]. MS is also heterogeneous clinically, and the disease can be divided into dif
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