Genes, environment, and susceptibility to multiple sclerosis

Multiple sclerosis (MS) is a chronic disease of the central nervous
system affecting young adults and thus representing a major burden
also for their families and communities. The etiology of MS is obscure
and its pathogenesis is yet incompletely depicted. Increased evidences
indicate a strong genetic contribution to MS susceptibility, although
others support the view that it is also influenced by environmental
factors, possibly related to still unidentified pathogens. MS appears to
be more heterogeneous than previously believed at the immunological
level, and new pathological studies indicate a series of subset of
conditions under the common denominator MS. The use of genetically
homogeneous and geographically isolated populations at high MS risk,
such as that of Sardinia, insular Italy, becomes in principle a vital
requirement to reduce biological variables and the intrinsic complexity
of the disease.
This review will focus on recent findings on the peculiarity of
Sardinian MS concerning epidemiological, genetic, and environmental
aspects. Epidemiological studies reveal a clear heterogeneous distribution
of MS cases in the Northern province of Sassari which may not
be uniquely assigned to genetic variations. Furthermore, a different
immunogenetic profile, including the association with other immunomediated
diseases, and a progressive change in clinical phenotype,
including age at onset, are present in this island which gives us
unexpected variations at the level of patients’ cohort and territorial
distribution, especially when the northern province is compared to the
southern one. This renders MS etiopathogenesis more complex than
formerly thought even in this selected and genetically stable
population.