Rheumatoid Arthritis: Barbet S

Michou L, Garnier S, Barbet S, Glikmans E, Ea HK, Uzan B, Asensio C, Ah Kioon MD, Lasbleiz S, Bardin T, Cornélis F, Lioté F. · Fédération de rhumatologie, Hôpital Lariboisière, Pôle Appareil Locomoteur, Assistance Publique-Hôpitaux de Paris, Paris, France. · Clin Exp Rheumatol. · Pubmed #19210874 No free full text.

Abstract: OBJECTIVE:Rheumatoid arthritis (RA) is characterized by hyperplasia of fibro-blast-like synoviocytes (FLSs), in part due to apoptosis resistance. Adrenomedullin, an anti-apoptotic peptide, is secreted more by RA than osteoarthritis FLSs. Adrenomedullin binds to a heterodimeric functional receptor, of calcitonin receptor-like receptor (CRLR) coupled with a receptor activity-modifying protein-2 (RAMP-2), which is also overexpressed by rheumatoid synoviocytes. Since adrenomedullin decreases RA FLS apoptosis, possibly contributing to the development of pannus, study of adrenomedullin and its receptor genes might reveal a linkage and association in French Caucasian RA trio families.METHODS:Within each of 100 families, one RA-affected patient and both parents underwent genotyping for polymorphisms of adrenomedullin, CRLR and RAMP-2, by PCR-restricted fragment-length polymorphism (RFLP) or Taqman 5' allelic discrimination assay. Statistical analysis relied on the transmission disequilibrium test, the affected family-based controls and the genotype relative risk. Haplotypes of CRLR were inferred, and linkage and association studies were performed.RESULTS:No significant transmission disequilibrium or association between the three genes and RA was observed. CRLR haplotypes revealed two major haplotypes, but no significant linkage with RA.CONCLUSION:Our findings provided no significant linkage or association of adrenomedullin and CRLR-RAMP-2 genes with RA in the studied trio families. The two CRLR polymorphisms rs3771076 and rs3771084 should be investigated in larger samples.

Jacq L, Garnier S, Dieudé P, Michou L, Pierlot C, Migliorini P, Balsa A, Westhovens R, Barrera P, Alves H, Vaz C, Fernandes M, Pascual-Salcedo D, Bombardieri S, Dequeker J, Radstake TR, Van Riel P, van de Putte L, Lopes-Vaz A, Glikmans E, Barbet S, Lasbleiz S, Lemaire I, Quillet P, Hilliquin P, Teixeira VH, Petit-Teixeira E, Mbarek H, Prum B, Bardin T, Cornélis F, Anonymous00262. · GenHotel-EA3886, Evry-Paris VII Universities, 91057 Evry-Genopole cedex, France. · Arthritis Res Ther. · Pubmed #17615072 links to  free full text

Abstract: The integrin alpha(v)beta3, whose alpha(v) subunit is encoded by the ITGAV gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the ITGAV gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the ITGAV gene for association and linkage to RA in a family-based study from the European Caucasian population. Two single nucleotide polymorphisms were genotyped by PCR-restriction fragment length polymorphism in 100 French Caucasian RA trio families (one RA patient and both parents), 100 other French families and 265 European families available for replication. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies (affected family-based controls), the transmission disequilibrium test, and the genotype relative risk.We observed a significant RA association for the C allele of rs3738919 in the first sample (affected family-based controls, RA index cases 66.5% versus controls 56.7%; P = 0.04). The second sample showed the same trend, and the third sample again showed a significant RA association. When all sets were combined, the association was confirmed (affected family-based controls, RA index cases 64.6% versus controls 58.1%; P = 0.005). The rs3738919-C allele was also linked to RA (transmission disequilibrium test, 56.5% versus 50% of transmission; P = 0.009) and the C-allele-containing genotype was more frequent in RA index cases than in controls (RA index cases 372 versus controls 339; P = 0.002, odds ratio = 1.94, 95% confidence interval = 1.3-2.9). The rs3738919-C allele of the ITGAV gene is associated with RA in the European Caucasian population, suggesting ITGAV as a new minor RA susceptibility gene.

Garnier S, Dieudé P, Michou L, Barbet S, Tan A, Lasbleiz S, Bardin T, Prum B, Cornélis F. · GenHotel-EA3886, Laboratoire Européen de Recherche pour la Polyarthrite Rhumatoïde, 2 rue Gaston Crémieux, 91057 Evry-Genopole Cedex, France. · Ann Rheum Dis. · Pubmed #17158136 No free full text.

Abstract: BACKGROUND: Recently, a new genetic factor within the interferon regulatory factor 5 (IRF5) gene was demonstrated for systemic lupus erythematosus (SLE) through linkage and association: the rs2004640-T allele. IRF5 is involved in the production of rheumatoid arthritis (RA) cytokines, and SLE already shares with RA one genetic factor within the tyrosine phosphatase PTPN22 gene. AIM: To test the hypothesis that the SLE IRF5 genetic factor could also be shared with RA. PATIENTS AND METHODS: 100 French Caucasian trio families with RA were genotyped and analysed with the transmission disequilibrium test, the frequency comparison of the transmitted and untransmitted alleles, and the genotype relative risk. 97% power was available to detect at least a trend in favour of a factor similar to that reported for SLE. RESULTS: The analysis showed the absence of linkage and association globally and in "autoimmune" RA subsets, with a weak non-significant trend against the IRF5 rs20046470-T allele. Given the robustness of familial-based analysis, this slight negative trend provided strong evidence against even a weaker factor than that reported for SLE. CONCLUSION: Our results exclude the IRF5 rs2004640-T allele as a major genetic factor for RA in this French Caucasian population.