RESUMO
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.
Assuntos
Artrite Reumatoide/genética , NF-kappa B/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Suscetibilidade a Doenças , Feminino , Frequência do Gene , Variação Genética , Haplótipos , Humanos , Quinase I-kappa B/genética , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de OligonucleotídeosRESUMO
OBJECTIVE: To investigate the possible association between the recently described interleukin 6 (IL-6) promoter polymorphisms at position -174, and susceptibility to ankylosing spondylitis (AS). METHODS: Ninety-two patients with AS, 157 healthy controls, and an additional group of 52 HLA-B27 positive unrelated individuals were included in this study. The -174 polymorphic site in the promoter region of IL-6 gene was typed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No statistically significant differences were observed when IL-6 promoter genotype and allele distribution between patients with AS and healthy controls were compared. CONCLUSION: Our results suggest the -174 IL-6 polymorphism does not play an important role in susceptibility to AS. Larger studies are needed to provide more conclusive evidence on the role of -174 IL-6 polymorphism in AS.