Rheumatoid Arthritis: Costas J

Dieguez-Gonzalez R, Akar S, Calaza M, Perez-Pampin E, Costas J, Torres M, Vicario JL, Velloso ML, Navarro F, Narvaez J, Joven B, Herrero-Beaumont G, Gonzalez-Alvaro I, Fernandez-Gutierrez B, de la Serna AR, Carreño L, Lopez-Longo J, Caliz R, Collado-Escobar MD, Blanco FJ, Fernandez-Lopez C, Balsa A, Pascual-Salcedo D, Gomez-Reino JJ, Gonzalez A. · Laboratorio de Investigacion 2 and Rheumatology Unit, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain. · Ann Rheum Dis. · Pubmed #18434448 No free full text.

Abstract: OBJECTIVE: To examine genetic association between rheumatoid arthritis (RA) and known polymorphisms in core genes of the nuclear factor (NF)kappaB pathway, the major intracellular pathway in RA pathogenesis. METHODS: Discovery and replication sample sets of Spanish patients with RA and controls were studied. A total of 181 single nucleotide polymorphisms (SNPs) uniformly spaced along the genomic sequences of 17 core genes of the NFkappaB pathway (REL, RELA, RELB, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, IKBKA, IKBKB, IKBKE, IKBKAP, KBRAS1, KBRAS2, MAP3K1, MAP3K14, TAX1BP1) were studied by mass spectrometry analysis complemented with 5'-nuclease fluorescence assays in the discovery set, 458 patients with RA and 657 controls. SNPs showing nominal significant differences were further investigated in the replication set of 1189 patients with RA and 1092 controls. RESULTS: No clear reproducible association was found, although 12 SNPs in IKBKB, IKBKE and REL genes showed significant association in the discovery set. Interestingly, two of the SNPs in the IKBKE gene, weakly associated in the discovery phase, showed a trend to significant association in the replication phase. Pooling both sample sets together, the association with these two SNPs was significant. CONCLUSION: We did not find any major effect among the explored members of the NFkappaB pathway in RA susceptibility. However, it is possible that variation in the IKBKE gene could have a small effect that requires replication in additional studies.

Costas J, Perez-Pampin E, Ferreiros-Vidal I, Torres M, Phillips C, Vicario JL, Pablos JL, Carracedo A, Gomez-Reino JJ, Gonzalez A. · Research Laboratory 2, Rheumatology Unit, and National Genotyping Center, Hospital Clinco Universitario de Santiago, 15706 Santiago de Compostela, Spain. · J Rheumatol. · Pubmed #16755651 No free full text.

Abstract: OBJECTIVE: To explore the role of single nuclear polymorphisms (SNP) in 2 candidate genes, SUMO4 and MAP3K7IP2, in susceptibility to rheumatoid arthritis (RA). METHODS: Two cohorts from different Spanish towns totalling 635 patients with RA and 826 controls were studied. Six SNP were genotyped by matrix assisted laser desorption-ionization time-of-flight (MALDI-TOF) with the MassARRAY SNP genotyping system. RESULTS: We found no association with susceptibility to RA for any of the SNP including a previously described functional variant in the SUMO4 gene (163A-->G). RA susceptibility was independent of the haplotypes defined by the 6 SNP and there was also no association with clinical features of RA. Conclusion. SUMO4 and MAP3K7IP2 SNP did not significantly influence predisposition to and features of RA, in contrast to previous genetic and functional evidence that suggested their involvement.