| Summary: | <p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is consistently associated with particular HLA-<it>DRB1</it>-<it>DQB1 </it>haplotypes. However, existing evidence suggests that variation at these loci does not entirely explain association of the HLA region with the disease. The <it>MOG </it>locus is a prime positional and functional candidate for such additional predisposing effects but the analysis is complicated by the strong, albeit labyrinthine pattern of linkage disequilibrium in the region. Here we have assessed the association of <it>MOG </it>variation with MS in the Sardinian population to see if it represents an independent contributor to MS predisposition.</p> <p>Results</p> <p>After re-sequencing the <it>MOG </it>gene in 21 healthy parents of MS patients we detected 134 variants, 33 of which were novel. A set of 40 informative SNPs was then selected and assessed for disease association together with 1 intragenic microsatellite in an initial data set of 239 MS families. This microsatellite and 11 SNPs were found to be positively associated with MS, using the transmission disequilibrium test, and were followed up in an additional 158 families (total families analysed = 397). While in these 397 families, 8 markers showed significant association with MS, through conditional tests we determined that these <it>MOG </it>variants were not associated with MS independently of the main <it>DRB1</it>-<it>DQB1 </it>disease associations.</p> <p>Conclusion</p> <p>These results indicate that variation within the <it>MOG </it>gene is not an important independent determinant of MS-inherited risk in the Sardinian population.</p>
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