Recherche de nouveaux facteurs génétiques de susceptibilité à la spondyloarthrite grâce à une approche associant études familiales et génomique fonctionnelle

Abstract : Spondyloarthritis (SpA) is a frequent and disabling chronic rheumatic disease. To date, more than 20 susceptibility loci have been identified, including HLA-B27 in the major histocompatibility complex (MHC). Most of the disease heritability remains to be elucidated. The aim of the study was to identify new genetic factors of susceptibility to SpA using an approach combining genetics and functional genomics. In the first part of this work, we genotyped SpA multiplex families with microarrays of 250,000 SNPs. Non parametric linkage analysis revealed a new locus significantly linked to SpA outside the MHC, in 13q13. Further studies on this locus allowed us to map the disease interval to a 1.3 Mb region, which will be soon sequenced. Moreover, family-based association study identified a significant association between one intronic SNP in MAPK14 and SpA. We also showed that one of the known ankylosing spondylitis-associated SNP in IL23R was indeed associated with sacroiliitis in SpA. We have also compared dendritic cells gene expression between nine SpA patients and ten controls and identified 81 genes differentially expressed. Moreover, we showed that ERAP1 gene expression (and at a less extent protein expression and enzymatic activity) is under the control of several polymorphisms in the gene which has previously been associated with SpA.
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Félicie Costantino. Recherche de nouveaux facteurs génétiques de susceptibilité à la spondyloarthrite grâce à une approche associant études familiales et génomique fonctionnelle. Génétique humaine. Université René Descartes - Paris V, 2014. Français. ⟨NNT : 2014PA05T056⟩. ⟨tel-01223109⟩

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