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.
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.
Authors: Johanna K Sandling; Sophie Garnier; Snaevar Sigurdsson; Chuan Wang; Gunnel Nordmark; Iva Gunnarsson; Elisabet Svenungsson; Leonid Padyukov; Gunnar Sturfelt; Andreas Jönsen; Anders A Bengtsson; Lennart Truedsson; Catharina Eriksson; Solbritt Rantapää-Dahlqvist; Anders Mälarstig; Rona J Strawbridge; Anders Hamsten; Lindsey A Criswell; Robert R Graham; Timothy W Behrens; Maija-Leena Eloranta; Gunnar Alm; Lars Rönnblom; Ann-Christine Syvänen Journal: Eur J Hum Genet Date: 2010-12-22 Impact factor: 4.246
Authors: Tanel Traks; Kati Koido; Roman Balõtšev; Triin Eller; Sulev Kõks; Eduard Maron; Innar Tõru; Jakov Shlik; Eero Vasar; Veiko Vasar Journal: Brain Behav Date: 2015-02-13 Impact factor: 2.708
Authors: Rebeca Dieguez-Gonzalez; Manuel Calaza; Eva Perez-Pampin; Alejandro Balsa; Francisco J Blanco; Juan D Cañete; Rafael Caliz; Luis Carreño; Arturo R de la Serna; Benjamin Fernandez-Gutierrez; Ana Maria Ortiz; Gabriel Herrero-Beaumont; Jose L Pablos; Javier Narvaez; Federico Navarro; Jose L Marenco; Juan J Gomez-Reino; Antonio Gonzalez Journal: Arthritis Res Ther Date: 2009-03-17 Impact factor: 5.156
Authors: Raquel López-Mejías; F David Carmona; Fernanda Genre; Sara Remuzgo-Martínez; Carlos González-Juanatey; Alfonso Corrales; Esther F Vicente; Verónica Pulito-Cueto; José A Miranda-Filloy; Marco A Ramírez Huaranga; Ricardo Blanco; Montserrat Robustillo-Villarino; Javier Rodríguez-Carrio; Mercedes Alperi-López; Juan J Alegre-Sancho; Verónica Mijares; Leticia Lera-Gómez; Eva Pérez-Pampín; Antonio González; Rafaela Ortega-Castro; Chary López-Pedrera; Mari L García Vivar; Catalina Gómez-Arango; Enrique Raya; Javier Narvaez; Alejandro Balsa; Francisco J López-Longo; Patricia Carreira; Isidoro González-Álvaro; Luis Rodríguez-Rodríguez; Benjamín Fernández-Gutiérrez; Iván Ferraz-Amaro; Oreste Gualillo; Santos Castañeda; Javier Martín; Javier Llorca; Miguel A González-Gay Journal: Arthritis Rheumatol Date: 2019-01-18 Impact factor: 10.995