Immunogenetics of multiple sclerosis: more questions than answers

Abstract

Multiple sclerosis (MS) is an immune-mediated chronic disease that affects mainly young people and usually evolves with progressive accumulation of disability in most patients over many years to decades 1 . There is a known latitudinal gradient of prevalence of MS: the higher the latitude, the farther away from the equator, the greater the number of affected people 2 . The existence of a latitude association for the development of MS brings with itself the influence of low sun exposure as a risk factor 3 . However, there are regions or ethnic groups in which, regardless of the latitude, people can present a greater or lesser risk of developing MS. Sardinians are well known exceptions as they present a much higher incidence of MS compared to the rest of Italy and even with other Mediterranean populations, which could be explained by genetic aspects 4 . On the other hand, regions in the far north of Norway have low incidences of MS compared to countries in the same latitude, pointing toward the influence of environmental factors more than genetic predisposition 5 . MS is a complex disease which is not triggered by a single factor but by the combination of genetic and environmental factors. Among the latter, in addition to the increased risk of developing MS by low levels of vitamin D (hence the relationship with sun exposure), obesity, smoking, EBV infection and excessive sodium intake in the diet are factors involved 6 . We must also mention the recent but not definitive studies of the relationship between gut microbiome and multiple sclerosis 7 . Regarding genetic factors, the question is not simple either and there is no single gene involved. From the scientific point of view, there are two possible types of genetic approach. The first and oldest of them is the study of the HLA system, which has established risk haplotypes in different populations with the knowledge already well established nowadays at an odds ratio of around 3 to develop MS in individuals with the allele HLA -DRB1*15: 01. However, the presence of this allele is neither sufficient nor necessary for the onset of MS because subjects without the allele can also develop the disease as well as many individuals carrying the risk allele who will never develop the disease. Another more recent approach is to study genes outside the HLA system identifying single-nucleotide polymorphisms (SNPs) through genome-wide association. So far, at least 57 SNPs that increase the risk of developing MS have been identified 8 . In this issue of Arquivos de Neuropsiquiatria, Werneck et al.9 chose to study the relationship between HLA alleles and the susceptibility to the development of MS in a population in Southern Brazil. The authors found a lower frequency than that described in European populations and even in Southeastern Brazil. The merit of the work was the use of highresolution technique for detection of HLA alleles. However, there are some problems which have been pointed out by the authors. First, the small number of cases included, which makes any considerat...

Association of Multiple Sclerosis Phenotypes with Single Nucleotide Polymorphisms of IL7R, LAG3, and CD40 Genes in a Jordanian Population: A Genotype-Phenotype Study

“…The global median prevalence of MS has increased from 30 to 33 cases per 100,000 people from 2008 to 2013 respectively [2,4]. Significantly, the prevalence rate of MS in Jordan increased to 39 per 100,000 people in the period from 2004 to 2005 [5][6][7][8].…”