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 (16646982)  |
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Validation of the reshaped shared epitope HLA-DRB1 classification in rheumatoid arthritis. |
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Laëtitia Michou1, Pascal Croiseau2, Elisabeth Petit-Teixeira1, Sophie Tezenas Du Montcel2, 3, Isabelle Lemaire1, 4, Céline Pierlot1, José Osorio1, Wafa Frigui1, Sandra Lasbleiz1, 5, Patrick Quillet1, 4, Thomas Bardin1, 5, Bernard Prum6, Françoise Clerget-Darpoux2, François Cornélis1, 5, 7, The European Consortium On Rheumatoid Arthritis Families |
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| résumé : |
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Recently, we proposed a classification of HLA-DRB1 alleles that reshapes the shared epitope hypothesis in rheumatoid arthritis (RA); according to this model, RA is associated with the RAA shared epitope sequence (72-74 positions) and the association is modulated by the amino acids at positions 70 and 71, resulting in six genotypes with different RA risks. This was the first model to take into account the association between the HLA-DRB1 gene and RA, and linkage data for that gene. In the present study we tested this classification for validity in an independent sample. A new sample of the same size and population (100 RA French Caucasian families) was genotyped for the HLA-DRB1 gene. The alleles were grouped as proposed in the new classification: S1 alleles for the sequences A-RAA or E-RAA; S2 for Q or D-K-RAA; S3D for D-R-RAA; S3P for Q or R-R-RAA; and X alleles for no RAA sequence. Transmission of the alleles was investigated. Genotype odds ratio (OR) calculations were performed through conditional logistic regression, and we tested the homogeneity of these ORs with those of the 100 first trio families (one case and both parents) previously reported. As previously observed, the S2 and S3P alleles were significantly over-transmitted and the S1, S3D and X alleles were under-transmitted. The latter were grouped as L alleles, resulting in the same three-allele classification. The risk hierarchy of the six derived genotypes was the same: (by decreasing OR and with L/L being the reference genotype) S2/S3P, S2/S2, S3P/S3P, S2/L and S3P/L. The homogeneity test between the ORs of the initial and the replication samples revealed no significant differences. The new classification was therefore considered validated, and both samples were pooled to provide improved estimates of RA risk genotypes from the highest (S2/S3P [OR 22.2, 95% confidence interval 9.9-49.7]) to the lowest (S3P/L [OR 4.4, 95% confidence interval 2.3-8.4]). |
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| domaine : |
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langue du texte
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Anglais |
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| ISSN : |
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1478-6362 |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1186/ar1949 |
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| journal : |
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| Arthritis Research and Therapy (Arthritis Res Ther) |
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BioMed Central |
| ISSN |
1478-6354 |
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| date de publication : |
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2006 |
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| volume : |
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8 |
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| page, identifiant, ... : |
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R79 |
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| contrat, financement : |
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This work was supported by Association Française des Polyarthritiques, Société Française de Rhumatologie, Association Rhumatisme et Travail, Association Polyarctique, Groupe Taitbout, Académie de Médecine, Association de Recherche sur la Polyarthrite, Genopole, Conseil Régional Ile de France, Fondation pour la Recherche Médicale, Université Evry-Val d'Essonne and unrestricted institutional support from Wyeth, Schering-Plough, Pfizer and Amgen. |
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