Abstract
BackgroundSouth-Western Sardinia (SWS) is a high risk area for Multiple Sclerosis (MS) with high prevalence and spatial clustering; its population is genetically representative of Sardinians and presents a peculiar environment. We evaluated the MS environmental risk of specific heavy metals (HM) and geographical factors such as solar UV exposure and urbanization by undertaking a population-based cross-sectional study in SWS.MethodsGeochemical data on HM, UV exposure, urbanization and epidemiological MS data were available for all SWS municipalities. Principal Component Analysis (PCA) was applied to the geochemical data to reduce multicollinearity and confounding criticalities. Generalized Linear Mixed Models (GLMM) were applied to evaluate the causal effects of the potential risk factors, and a model selection was performed using Akaike Information Criterion.ResultsThe PCA revealed that copper (Cu) does not cluster, while two component scores were extracted: 'basic rocks', including cobalt, chromium and nickel, and 'ore deposits', including lead and zinc. The selected multivariable GLMM highlighted Cu and sex as MS risk factors, adjusting for age and 'ore deposits'. When the Cu concentration increases by 50 ppm, the MS odds are 2.827 (95% CI: 1.645; 5.07) times higher; females have a MS odds 2.04 times (95% CI: 1.59; 2.60) higher than males.ConclusionsThe high frequency of MS in industrialized countries, where pollution by HM and CO poisoning is widespread, suggests a relationship between environmental exposure to metals and MS. Hence, we suggested a role of Cu homeostasis in MS. This is a preliminary study aimed at generating hypotheses that will need to be confirmed further.
Highlights
The Principal Component Analysis (PCA) revealed that copper (Cu) does not cluster, while two component scores were extracted: ’basic rocks’, including cobalt, chromium and nickel, and ’ore deposits’, including lead and zinc
When the Cu concentration increases by 50 ppm, the Multiple Sclerosis (MS) odds are 2.827 times higher; females have a MS odds 2.04 times higher than males
The etiology of multiple sclerosis (MS) is still unknown, but it is commonly believed that genetic susceptibility combined with exposure to environmental factors are required for its development
Summary
The etiology of multiple sclerosis (MS) is still unknown, but it is commonly believed that genetic susceptibility combined with exposure to environmental factors are required for its development. [1] MS has an increasing incidence in populations residing at higher latitudes [2,3], and a rise in its incidence has been seen almost worldwide in the last decades, [4] pointing to the importance of changes in the environment (e.g., transition from rural to urban living, lifestyle changes) [5] interacting with a permissive genetic background.Many genetic factors have been discovered in recent years [6], while environmental factors have been somewhat poorly identified, with the slight exception of Epstein Barr Virus (EBV), smoke, Ultraviolet (UV) exposure and vitamin D. [7,8,9]Pollution and exposures to heavy metals (HM) are suspected of being involved in the pathogenesis and/or progression of various neurological diseases [10,11,12], including MS. [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28]Among such HM, aluminium (Al), barium (Ba), calcium (Ca), cadmium (Cd), copper (Cu), iron (Fe), lead (Pb), mercury (Hg), magnesium (Mg) and zinc (Zn) have been studied in MS, in different biological materials, by some case-control studies, [16,17,18,19,20,21,22,23,24] with not univocal results. The SWS area is rich in mineral deposits These occurrences, arranged from the oldest to the most recent, include: i) Pb-Zn-Ba mineralisations related to Cambrian carbonatic rocks, (a large number of ore-bodies in the so-called “metalliferous ring”); ii) mineralisations with barite, iron oxides, Pb and Zn sulphides and oxides; iii) lode mineralisations with Pb, Zn, Ag and F; iv) skarns with mixed sulphides (Cu etc) and Fe; v) remobilised post-Hercynian mineralisations with Ba, Pb, Zn, Ag in Cambrian limestones. South-Western Sardinia (SWS) is a high risk area for Multiple Sclerosis (MS) with high prevalence and spatial clustering; its population is genetically representative of Sardinians and presents a peculiar environment. We evaluated the MS environmental risk of specific heavy metals (HM) and geographical factors such as solar UV exposure and urbanization by undertaking a population-based cross-sectional study in SWS
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