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Arch Hellen Med, 25(2), March-April 2008, 135-150


Recent findings in the genetics of multiple sclerosis

Department of Neurology, University of Athens, "Aeginition" Hospital, Athens, Greece

The pathogenesis of multiple sclerosis (MS) is influenced by both genetic and environmental factors. Genetic factors can affect MS susceptibility or clinical expression. Findings from well-designed, population-based epidemiological studies in the past 20 years (family, twin, adoptee, half-sibling and conjugal MS studies) have clarified the contribution of genetic factors to MS susceptibility. At the molecular level, candidate gene association studies of the past 15 years have correlated specific HLA gene haplotypes with the disease. Genome-wide linkage studies in the past 10 years, especially the recently completed high-density linkage study, have made clear that, apart from the HLA locus, the contribution of other genes to susceptibility is limited. In the past 5 years, therefore, it has been widely accepted that the future of MS genetic research lies with association studies, which are more powerful for identifying genes with moderate contribution to risk. Based on recent DNA microarray technology, the first genome-wide association (linkage disequilibrium) screens in MS have been completed. The findings, published in 2003, confirmed the results of linkage studies and further identified genomic regions of possible importance for disease susceptibility. Studies in larger patient cohorts using much higher density markers are under way, and their results are eagerly awaited in the near future. Well-designed candidate gene studies in large patient cohorts have also been completed recently and have identified new possible MS susceptibility genes. Ás a result of the higher patient numbers studied and the further analysis of clinical parameters of MS, over the last 10 years an increased and in-depth study of the genetic influence on disease expression has been witnessed. Although definite conclusions cannot yet be drawn, the most interesting findings concern the influence of HLA and apolipoprotein E on significant disease parameters, such as disease course and severity. Factors that will be important in the future include accounting for the clinical heterogeneity of MS and studying genetically isolated populations, in an effort to enhance the contribution of different genetic factors.

Key words: Association study, Gene, Genetics, Linkage study, Multiple sclerosis.

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