Multiple sclerosis: pathogenesisTuesday, June 23, 2009, 14:00 - 14:15Replication phase of a whole-genome association study in progressive forms of multiple sclerosisF. Martinelli Boneschi, F. Esposito, J. Wojcik, A. Ghezzi, R. Capra, M. Rodegher, V. Martinelli, B. Colombo, L. Moiola, E. Lindstrom, J. Hillert, J. Rubio, T.J. Kilpatrick, B.V. Taylor, H. Abderrahim, G. Comi (Milan, IT; Geneva, CH; Varese, Brescia, IT; Stockholm, SE; Melbourne, AU)
Objectives: The clinical heterogeneity of multiple sclerosis (MS) can be partly explained by genetic factors. The aim of this study is the genetic characterization of the progressive forms of MS.
Methods: We applied a genome-wide high-density single-nucleotide polymorphism (SNP) genotyping approach (Affymetrix 500k chip) in 197 patients affected with the less common course of primary progressive (PPMS), progressive-relapsing (PRMS) and single attack progressive (SAP) multiple sclerosis and 234 age- and sex-matched controls. We also tested the association with HLA DRB1*1501 in this group of patients.
Results: The HLA class II region was confirmed to be strongly associated with progressive forms of MS (odds ratio: 2.71, 95% C.I. 1.36-5.40). Moreover, additional markers in several genes, including DPP6, NRG1, have been found to be associated (p< 10-4) with progressive MS.
We are replicating best hits of this preliminary study on additional independent case-controls samples of progressive MS patients.
Conclusion: The selection of more clinically homogeneous phenotype at the cost of a lower sample size could represent an alternative strategy for the identification of causative genetic variants in MS.
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