title: Haplotype structure of TNFRSF5-TNFSF5 (CD40-CD40L) and association analysis in systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that is caused by genetic and environmental factors. The tumour necrosis factor (TNF) superfamily of genes play a central role in immune regulation and have been proposed to be involved in the development of SLE. TNFRSF5 (CD40) falls on 20q11-13, a region linked with SLE in three independent genome-wide studies. TNFSF5 (CD40L) falls on Xq26 and is the ligand for TNFRSF5. Seven single-nucleotide polymorphisms (SNPs) in CD40 and eight SNPs in CD40L were looked at for linkage disequilibrium (LD) and haplotype analysis in European-Caucasians. Limited haplotype diversity was observed across CD40 and CD40L, and >97% of the diversity was captured. We also examined the association of SNPs and haplotypes in CD40 and CD40L with SLE in European-Caucasians. There was no evidence of association for CD40 or CD40L in 408 European-Caucasian families with SLE from UK. Haplotype tagging SNPs (htSNPs) are made known, which will facilitate analysis for susceptibility in other autoimmune diseases and risk for infectious disease.
authors.affiliation: Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Sapna
authors.initials: S
authors.lastname: Chadha
authors.forename: Katie
authors.initials: K
authors.lastname: Miller
authors.forename: Lisa
authors.initials: L
authors.lastname: Farwell
authors.forename: Liz B
authors.initials: LB
authors.lastname: Lightstone
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: John D
authors.initials: JD
authors.lastname: Rioux
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vyse
mesh_terms: D019013:CD40 Antigens / Q000235:genetics*; D023201:CD40 Ligand / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide; D006113:United Kingdom; D044465:White People / Q000235:genetics
chemical_list: D019013:CD40 Antigens; D023201:CD40 Ligand