| Summary: | Environmental and genetic factors are assumed to be necessary for the development of multiple sclerosis (MS), however its interactions are still unclear. For this reason here, we have not only analyzed the impact on increased risk of MS of the best known factors (<i>HLA-DRB1*15:01</i> allele, sun exposure, vitamin D levels, smoking habit), but we have included another factor (skin phototype) that has not been analyzed in depth until now. This study included 149 MS patients and 147 controls. A multivariate logistic regression (LR) model was carried out to determine the impact of each of the factors on the increased risk of MS. Receiver Operating Characteristics (ROC) analysis was performed to evaluate predictive value of the models. Our multifactorial LR model of susceptibility showed that females with light brown skin (LBS), smokers and who had <i>HLA-DRB1*15:01</i> allele had a higher MS risk (LBS: OR = 5.90, IC95% = 2.39–15.45; smoker: OR = 4.52, IC95% = 2.69–7.72; presence of <i>HLA-DRB1*15:01</i>: OR = 2.39, IC95% = 1.30–4.50; female: OR = 1.88, IC95% = 1.08–3.30). This model had an acceptable discriminant value with an Area Under a Curve AUC of 0.76 (0.69–0.82). Our study indicates that MS risk is determined by complex interactions between sex, environmental factors, and genotype where the milieu could provide the enabling proinflammatory environment that drives an autoimmune attack against myelin by self-reactive lymphocytes.
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