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.
Sotgiu
Stefano
S
Institute of Clinical Neurology, University of Sassari, 07100 Sassari, Italy. stefanos@uniss.it
Pugliatti
Maura
M
Fois
Maria Laura
ML
Arru
Giannina
G
Sanna
Alessandra
A
Sotgiu
Maria Alessandra
MA
Rosati
Giulio
G
D004198:Disease Susceptibility; D004777:Environment; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D010802:Phylogeny; D015995:Prevalence