Replication of the TNFSF4 (OX40L) promoter region association with systemic lupus erythematosus.

Genes Immun 2009 Apr 18;10(3):248-53. Epub 2008 Dec 18.

Department of Genetics and Pathology, Rudbeck Laboratory, University of Uppsala, Sweden.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/gene.2008.95DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867640PMC
April 2009
5 Reads

Publication Analysis

Top Keywords

systemic lupus
8
lupus erythematosus
8
upstream region
8
alleles snps
8
association single
8
association tnfsf4
8
snps rs1234317
8
association
7
1312 cases
4
tested 1312
4
cases 1801
4
association analysis
4
1801 controls
4
italy spain
4
major alleles
4
spain argentina
4
germany italy
4
rs1234317 rs12039904
4
rs12039904 association
4
controls germany
4

Similar Publications