title: Replication of the TNFSF4 (OX40L) promoter region association with systemic lupus erythematosus.
abstract: The tumor necrosis factor ligand superfamily member 4 gene (TNFSF4) encodes the OX40 ligand (OX40L), a costimulatory molecule involved in T-cell activation. A recent study demonstrated the association of TNFSF4 haplotypes located in the upstream region with risk for or protection from systemic lupus erythematosus (SLE). To replicate this association, five single nucleotide polymorphisms (SNPs) tagging the previously associated haplotypes and passing the proper quality-control filters were tested in 1312 cases and 1801 controls from Germany, Italy, Spain and Argentina. The association of TNFSF4 with SLE was replicated in all the sets except Spain. There was a unique risk haplotype tagged by the minor alleles of the SNPs rs1234317 (pooled odds ratio (OR)=1.39, P=0.0009) and rs12039904 (pooled OR=1.38, P=0.0012). We did not observe association to a single protective marker (rs844644) or haplotype as the first study reported; instead, we observed different protective haplotypes, all carrying the major alleles of both SNPs rs1234317 and rs12039904. Association analysis conditioning on the haplotypic background confirmed that these two SNPs explain the entire haplotype effect. This first replication study confirms the association of genetic variation in the upstream region of TNFSF4 with susceptibility to SLE.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, University of Uppsala, Sweden.
authors.forename: Angélica M
authors.initials: AM
authors.lastname: Delgado-Vega
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, University of Uppsala, Sweden.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Abelson
authors.affiliation: Instituto de Biomedicina "López-Neyra", CSIC, Granada, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Sánchez
authors.affiliation: Medical School Hannover, Hannover, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
authors.affiliation: Department of Medical Sciences and IRCAD, University of Eastern Piedmont, Novara, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.affiliation: Department of Clinical Medicine, Rheumatology Unit, Siena University, Siena, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Galeazzi
authors.affiliation: Servicio Medicina Interna, Hospital Virgen de las Nieves, Granada.
authors.forename: Juan
authors.initials: J
authors.lastname: Jiménez-Alonso
authors.affiliation: Sanatorio Parque, Rosario, Argentina.
authors.forename: Bernardo A
authors.initials: BA
authors.lastname: Pons-Estel
authors.affiliation: Instituto de Biomedicina "López-Neyra", CSIC, Granada, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, University of Uppsala, Sweden.|Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
authors.forename: Marta E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D053278:OX40 Ligand / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic
chemical_list: D053278:OX40 Ligand