Portal de Periódicos da CAPES

Genetic variation in the nuclear factor κB pathway in relation to susceptibility to rheumatoid arthritis

2008; BMJ; Volume: 68; Issue: 4 Linguagem: Inglês

10.1136/ard.2007.087304

1468-2060

Rebeca Dieguez‐Gonzalez, Servet Akar, Manuel Calaza, Eva Pérez‐Pampín, Javier Costas, María Torres, José L. Vicário, M L Velloso, Federico Navarro, Javier Narváez, Beatriz Joven, Gabriel Herrero‐Beaumont, Isidoro González‐Álvaro, Benjamín Fernández‐Gutiérrez, Arturo Rodríguez de la Serna, Luis Orlando Duitama Carreño, José Javier López-Longo, Rafael Cáliz, María Dolores Collado-Escobar, Francisco J. Blanco, C. Fernández-López, Alejandro Balsa, Dora Pascual‐Salcedo, Juan J. Gómez‐Reino, Antonio González,

interferon and immune responses

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.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.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.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.