RESUMEN
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.
Asunto(s)
Artritis Reumatoide/genética , FN-kappa B/genética , Polimorfismo de Nucleótido Simple , Adulto , Estudios de Casos y Controles , Susceptibilidad a Enfermedades , Femenino , Frecuencia de los Genes , Variación Genética , Haplotipos , Humanos , Quinasa I-kappa B/genética , Funciones de Verosimilitud , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
Chronic interstitial cystitis (CIC) has been thought to result from autoimmune phenomena and its occurrence in systemic lupus erythematosus (SLE) has occasionally been recorded. We report a patient with SLE whose initial urinary symptoms were caused by CIC. Two of 3 patients (including ours) whose cases have been reported also had diarrhea, a common symptom in idiopathic CIC. All 3 patients had cutaneous and/or bladder vasculitis. CIC occurring in SLE seems to be due to immune complex deposition.
