Abstract EN:

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. It is widely believed to occur in genetically susceptible individuals after exposure to undefined environmental factors that influence epigenetic factors. These factors may act at two different levels: (1) on the susceptibility to develop MS and (2) on response to MS treatment Genetic association studies identified rs34536443polymorphism in TYK2 gene associated with MS susceptibility, and we confirmed this association in the French population. Rs34536443 polymorphism localizes in the exon 21 of TYK2 gene, and codes either a proline (major allele) or an alanine at position 1104, in the tyrosine kinase. A functional consequence of this polymorphism could be to alter kinase function of this protein. Moreover, TYK2 deficiency revealed an important role in immunity and in lymphocyte differentiation. Given these data, we investigated the potential functional consequences of the rs34536443 polymorphism on TYK2 activation, and in lymphocyte polarization. After MS development, genetic factors may influence patient response to treatment. IFN? was the first therapy proposed with a demonstrated efficacy in MS. With the development of new drugs, it will be of importance to personalise medicine. Hence, exploring the degree of variability in candidate genes for direct association with treatment response represents a promising approach to improve the overall efficacy of the treatment. In a preliminary study, significant associations with OAS1 and TRAIL polymorphisms were found suggesting that genetic variants in these two genes may be of clinical interest in MS as predictors of the efficacy to IFN? therapy.