Protective and Risk Factors in Multiple Sclerosis

Abstract

Introduction Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system (CNS). Damage to myelin proteins occurs during MS progression and relapse. Over 2 million people suffer from the consequences of pathological mechanisms which MS involves, monocular visual loss, limb weakness/sensory loss, diplopia (double vision) and ataxia resulting from optic neuritis, transverse myelitis, brainstem dysfunction, and cerebellar lesions being among them. 1 Based on the disease course, MS patients can be divided into four main types: I) Relapsing-remitting MS (RRMS), which is by far the most common type, affecting about 85% of MS patients; II) Secondary progressive MS (SPMS), which may progress in patients with relapsingremitting MS; III) Primary progressive MS (PPMS); and IV) Progressive-relapsing MS (PRMS). 2 A recently detected subtype of the disease described as "myelocortical MS" argues against the idea that neural degeneration necessarily occurs following demyelination. In patients with myelocortical MS, demyelinated lesions in cerebral white matter were not observed. Similar to typical MS courses, however, the mean cortical neuronal densities were significantly lower than those of the healthy controls. 3 These new findings will further improve the diagnoses and treatments utilized in MS patients. Genetic Factors Human Leukocyte Antigen and microRNAs Genes The human leukocyte antigen (HLA)-DRB1 gene explains up to 10.5% of the genetic variance underlying risk. 4 HLA-DRB1*15:01 allele has the strongest association with increased MS risk among genetic risk factors and has been consistently associated with MS susceptibility in approximately all populations studied, pointing to a specific antigen presentation as the pathogenic mechanism. Based on previous studies, the association between MS and the HLA-DR15 haplotype (HLA-DRB1*15:01 allele and the alleles in linkage disequilibrium with it; HLA-DQB1*0602 and HLA-DQA1*0102) has been shown throughout both European and non-European populations, 5 except in Sardinian individuals, among whom MS susceptibility has been reported to be associated with HLA-DR4 (DRB1*0405, DQA1*0301, DQB1*0302) instead of HLA-DR15. 5-7 The association between HLA-DR2 and MS has been observed mostly among northern European populations. 8 A single vitamin D response element was identified in the HLA-DRB1 promoter region, advancing the idea of an interaction between vitamin D and HLA-DRB1. The role of this interaction in disease etiology has not been elucidated yet, but it can be hypothesized that a lack of vitamin D in early childhood can alter the expression levels of HLA