Tesis doctoral de Nieves Perdigones Borderias
Resumen en inglés rheumatoid arthritis (ra) is a chronic inflammatory autoimmune disease affecting aproximately 1 of european and western populations. Although its aetiology remains elusive, it is known that genetic and environmental factors trigger disease development and severity. Both factors are being differentialy associated with ra subphenotypes. Therefore, the hypothesis has been raised that differential pathways explain ra disease in different subgroups of ra patients which are mainly c lasified by the presence/absence of anti-cyclic citrullinated peptides (anti-ccp) autoantibodies. Heritability of ra is estimated in aproximately 60 , being the major contributor located on the hla-drb1 gene (40 of total heritability). Further studi es have revealed the existence of other non-hla genetic risk factors associated with ra. However, over 50 of ra heritability remains to be explained. Herein we have attempted to contribute to expand the genetic knowledge of ra by performing associat ion studies in ra patients and different subphenotypes by analysing single nucleotide polymorphisms (snps) and microsatellites. Marker choice was performed on the basis of, first a candidate gene approach and secondly, the findings of genome wide ass ociation studies (gwas). Finally, we have analyzed genetic interactions by hypothesis-driven and hypothesis-free studies. the candidate gene approach has been widely used, leading to the description of well known ra susceptibility loci, such as ptpn 22, stat4, padi4 and ctla4. Marker choice is based on previous knowledge of the biochemical basis of the disease provided by: animal models, purified protein levels, mrna differential expression, previous linkage analyses and/or their association to other autoimmune diseases. Accordingly, we consider that the genes capsl/il7r, cd40, ptger4 and ciita/clec16a/socs1, are well worthy of study on ra susceptibility. In contrast to candidate gene studies, and now dominating the genetic research area, g was are hypothesis-free analyses genotyping over 500,000 snps along the genome. These hypothesis-free studies have described the association of numerous markers located on the following genetic regions: traf1/c5, olig3/tnfaip3, cd40, tnfrsf14, prkcq, ccl21, cdk6, kif5a/pip4k2c, il2rb, cd28, il2/il21, cd2/cd58, prdm1/blimp1, ptprc, traf6/rag1, fcgr2a and rel. However, an isolated description of association is not enough to warrant its reliability. Replication is consequently very important for t
Datos académicos de la tesis doctoral «Estudio del genes de suceptibilidad no-hla implicados en artritis reumatoide en población española«
- Título de la tesis: Estudio del genes de suceptibilidad no-hla implicados en artritis reumatoide en población española
- Autor: Nieves Perdigones Borderias
- Universidad: Complutense de Madrid
- Fecha de lectura de la tesis: 18/06/2010
Dirección y tribunal
- Director de la tesis
- Elena Urcelay García
- Tribunal
- Presidente del tribunal: María pilar Iniesta serrano
- trinidad Caldés llopis (vocal)
- laura susana Murillo ruiz (vocal)
- Javieralberto Carbone campoverde (vocal)