Article Text

other Versions

PDF
Genetic variation in the NFκB pathway in relation to susceptibility to rheumatoid arthritis
  1. Rebeca Dieguez-Gonzalez (rebecadg{at}usc.es)
  1. Hospital Clinico Universitario de Santiago, Spain
    1. Servet Akar (servet.akar{at}hotmail.com)
    1. Hospital Clinico Universitario de Santiago, Spain
      1. Manuel Calaza (mcalaza{at}gmail.com)
      1. Hospital Clinico Universitario de Santiago, Spain
        1. Eva Perez-Pampin (evappampin{at}gmail.com)
        1. Hospital Clinico Universitario de Santiago, Spain
          1. Javier Costas (bfcostas{at}usc.es)
          1. Hospital Clinico Universitario de Santiago, Spain
            1. Maria Torres (matorres{at}usc.es)
            1. Hospital Clinico Universitario de Santiago, Spain
              1. Jose Luis Vicario (jlvicario{at}hotmail.com)
              1. Regional Transfusion Center, Spain
                1. Maria Luisa Velloso (mlvelloso{at}hotmail.com)
                1. Hospital Universitario de Valme, Spain
                  1. Federico Navarro (federiconavarro{at}supercable.es)
                  1. Hospital Universitario Virgen Macarena, Spain
                    1. Javier Narváez (31577edd{at}comb.es)
                    1. Hospital Universitario de Bellvitge, Spain
                      1. Beatriz Esther Joven (bejoven.hdoc{at}salud.madrid.org)
                      1. "12 Octubre" Hospital, Spain
                        1. Gabriel Herrero-Beaumont (gherrero{at}fjd.es)
                        1. Fundacion Jimenez Diaz, Spain
                          1. Isidoro Gonzalez-Alvaro (isidoro.ga{at}ser.es)
                          1. Hospital Universitario La Princesa, Spain
                            1. Benjamin Fernandez-Gutierrez (bfernandez.hcsc{at}salud.madrid.org)
                            1. Hospital Clinico San Carlos, Spain
                              1. Arturo R de la Serna (arturojj{at}hotmail.com)
                              1. Hospital Santa Creu e San Pau, Spain
                                1. Luis Carreño (lcarreno.hgugm{at}salud.madrid.org)
                                1. Hospital Universitario Gregorio Marañon, Spain
                                  1. Javier Lopez-Longo (flopezlon.hgugm{at}salud.madrid.org)
                                  1. Hospital Universitario Gregorio Marañon, Spain
                                    1. Rafael Caliz (rcaliz{at}fundacionhvn.org)
                                    1. Hospital Universitario Virgen de las Nieves, Spain
                                      1. Maria Dolores Collado-Escobar (mdcollado{at}fundacionhvn.org)
                                      1. Hospital Universitario Virgen de las Nieves, Spain
                                        1. Francisco J Blanco (francisco_blanco{at}canalejo.org)
                                        1. CHU Juan Canalejo, Spain
                                          1. Carlos Fernandez-Lopez (jferlop1{at}canalejo.org)
                                          1. Hospital Universitario Juan Canalejo, Spain
                                            1. Alejandro Balsa (al.balsa{at}telefonica.net)
                                            1. Hospital La Paz, Spain
                                              1. Dora Pascual-Salcedo (dpascual.hulp{at}salud.madrid.org)
                                              1. "La Paz" Hospital, Spain
                                                1. Juan J Gomez-Reino (juan.jesus.gomez-reino.carnota{at}sergas.es)
                                                1. Hospital Clinico Universitario de Santiago, Spain
                                                  1. Antonio Gonzalez (antonio.gonzalez.martinez-pedrayo{at}sergas.es)
                                                  1. Hospital Clinico Universitario de Santiago, Spain

                                                    Abstract

                                                    Objective: To examine genetic association between RA and known polymorphisms in core genes of the NFκB pathway, the major intracellular pathway in RA pathogenesis.

                                                    Methods: Discovery and replication sample sets of Spanish RA patients and controls were studied. A total of 181 single nucleotide polymorphisms (SNPs) uniformly spaced along the genomic sequences of 17 core genes of the NFκB 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 RA patients and 657 controls. SNPs showing nominal significant differences were further investigated in the replication set of 1189 RA patients 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 NFκB 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.

                                                    Statistics from Altmetric.com

                                                    • Web only appendix 68:4;579

                                                      Request permissions

                                                      If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.