**Genetic and Biochemical Factors Related to the Risk and Disability Progression in Multiple Sclerosis**

Daniel Čierny, Jozef Michalik, Ema Kantorová, Egon Kurča and Ján Lehotský

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/63468

#### **Abstract**

Sclerosis multiplex (multiple sclerosis, MS) is a chronic autoimmune inflammatory disease of the central nervous system. The immune regulatory defects lead to the process of inflammation and neurodegenerationthat results in the deterioration of neurological functions. It is still unclear as to why MS is so devastating and rapidly progressive in one patient and less so in another. It is known that the etiopathogenesis of MS is very complex, and many factors can be involved in the risk and character of the disease and its progression. In this chapter, we discuss the general molecular and cellular mechanisms of action of genetic and biochemical factors that are related to immune system regulation and thus can be connected to the individually varying risk and disability progression of MS. We found that gene variants of the gene polymorphism rs6897932 in interleukin 7 receptor α chain gene rs10735810 in vitamin D receptor gene and *HLA-DR* and *HLA-DQ* genes as well as the serum level of vitamin D are associated with MS risk or disability progres‐ sion in Central European Slovak population.

**Keywords:** multiple sclerosis, risk, disability progression, gene polymorphism, bio‐ chemical marker

#### **1. Introduction**

In triggering an autoimmune response in multiple sclerosis (MS), environmental factors have a strong effect and interact with complex risk-conferring genetic variants [1–3]. In this process, the myelin reactive Tcells with altered functional characteristics are formed and

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activated [4]. The immune regulatory defects and increased migration of autoreactive lymphocytes within the brain, that are the typical traits in MS, lead to the process of inflammation, myelin sheath breakdown, demyelination, remyelination, neuronal and axonal degeneration, and subsequent deterioration of neurological functions [5]. Neurodegenera‐ tion, neuronal and axonal damage that correlate with the progression of the disease can be a process partly independent from inflammation and demyelination or even can be the cause of demyelination occurring from the disease onset. Axonal damage in MS is a result of many pathological processes [6, 7].

It is still unclear as to why MS is so devastating and rapidly progressive in one patient and less so in another. Because the etiopathogenesis of MS is very complex, disease develop‐ ment as well as the characteristics of disease progression is probably the consequence of multifactorial interaction. Our work is dedicated to genetic and biochemical markers that were chosen according to their possible role in the modulation of the immune response in MS patients and thus could be associated with MS risk and disability progression. In our work, we discuss the immune response-related genetic factors associated with MS that can be generally classified into *HLA* genes and *non-HLA* genes. Since vitamin D can have an important role in the pathogenesis of MS, great part of our work is dedicated to its metabo‐ lism, functions, mechanisms of action in MS and genetic factors that can modify these effects. In this work, we also present the results of our own analysis of genetic and biochemical markers that we found to be associated with MS risk or progression in the group consist‐ ing of MS patients with clinically diagnosed MS and healthy individuals from the region of Central Slovakia. To evaluate the disease progression rate, we used the widely accepted multiple sclerosis severity score (MSSS, score range 0.01–9.99) [8] that considers the neuro‐ logical impairment of the functional systems (expanded disability status scale score) [9] together with disease duration. For the purpose of the association analysis of these mark‐ ers with the rate of disease disability progression, we stratified MS patients by MSSS scores to three groups—slowly progressing MS (MSSS < 3), mid-rate progressing MS (MSSS 3–6) and rapidly progressing MS (MSSS > 6) [10].
