| Summary: | <p>Abstract</p> <p>Background</p> <p>The etiology of multiple sclerosis (MS) is at present not fully elucidated, although it is considered to result from the interaction of environmental and genetic susceptibility factors. In this work we aimed at testing the Early B-cell Factor (<it>EBF1</it>) gene as a functional and positional candidate risk factor for this neurological disease. Axonal damage is a hallmark for multiple sclerosis clinical disability and EBF plays an evolutionarily conserved role in the expression of proteins essential for axonal pathfinding. Failure of B-cell differentiation was found in EBF-deficient mice and involvement of B-lymphocytes in MS has been suggested from their presence in cerebrospinal fluid and lesions of patients.</p> <p>Methods</p> <p>The role of the <it>EBF1 </it>gene in multiple sclerosis susceptibility was analyzed by performing a case-control study with 356 multiple sclerosis patients and 540 ethnically matched controls comparing the <it>EBF1 </it>polymorphism rs1368297 and the microsatellite <it>D5S2038.</it></p> <p>Results</p> <p>Significant association of an <it>EBF1</it>-intronic polymorphism (rs1368297, A vs. T: p = 0.02; OR = 1.26 and AA vs. [TA+TT]: p = 0.02; OR = 1.39) was discovered. This association was even stronger after stratification for the well-established risk factor of multiple sclerosis in the Major Histocompatibility Complex, DRB1*1501 (AA vs. [TA+TT]: p = 0.005; OR = 1.78). A trend for association in the case-control study of another <it>EBF1 </it>marker, the allele 5 of the very informative microsatellite <it>D5S2038</it>, was corroborated by Transmission Disequilibrium Test of 53 trios (p = 0.03).</p> <p>Conclusion</p> <p>Our data support <it>EBF1 </it>gene association with MS pathogenesis in the Spanish white population. Two genetic markers within the <it>EBF1 </it>gene have been found associated with this neurological disease, indicative either of their causative role or that of some other polymorphism in linkage disequilibrium with them.</p>
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