title: A candidate gene analysis of three related photosensitivity disorders: cutaneous lupus erythematosus, polymorphic light eruption and actinic prurigo.
abstract: BACKGROUND
  Polymorphic light eruption (PLE) is a common inherited photosensitivity disorder, which may predispose to several related but distinct conditions, including subacute cutaneous lupus erythematosus (SCLE), discoid lupus erythematosus (DLE) and actinic prurigo (AP).
  
  
  OBJECTIVE
  To examine specific candidate genes for shared susceptibility alleles between these related phenotypes.
  
  
  METHODS
  Eighty-five caucasian patients with annular SCLE or DLE were recruited, in addition to 102 first-degree relatives. The prevalence of PLE in both the patient and relative groups was determined by detailed interview and clinical examination. Eighty-five patients with pure PLE and 59 patients with AP were also recruited. Candidate genes were analysed by typing of single nucleotide polymorphisms of IL10 (-1082 G/A and -819 C/T), FCGR2A (131 R/H), SELE (128 S/R), ICAM1 (241 G/R and 469 E/K), IL1A (+ 4845 G/T), IL1B (-511 C/T and + 3954 C/T), IL1RN (+ 2018 T/C) and TNF (-308 G/A) using polymerase chain reaction (PCR) with sequence-specific primers and 5'-nuclease PCR.
  
  
  RESULTS
  A significant association was found between SCLE and the rare TNF -308 A allele when compared with patients with DLE (P = 0.043), PLE (P = 0.001), AP (P < 0.001) and healthy controls (P < 0.001). However, there was strong linkage disequilibrium between TNF -308 A and the HLA A*01, B*08, DRB1*0301 haplotype. A negative association was also found between SCLE and the IL1B + 3954 T allele (P = 0.039), but the significance was lost on correction for multiple testing.
  
  
  CONCLUSIONS
  We have demonstrated the association of SCLE with the rare TNF -308 A allele, which may be pathogenic or, alternatively, a marker allele for the extended HLA A*01, B*08, DRB1*0301 haplotype that is associated with a number of autoimmune conditions. Although many of the other loci that we chose failed to demonstrate an association, a candidate gene approach remains the most logical one, and the most likely to yield positive results in the future.
authors.affiliation: Department of Photobiology, St. John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, UK. thomas.millard@kcl.ac.uk
authors.forename: T P
authors.initials: TP
authors.lastname: Millard
authors.forename: E
authors.initials: E
authors.lastname: Kondeatis
authors.forename: A
authors.initials: A
authors.lastname: Cox
authors.forename: A G
authors.initials: AG
authors.lastname: Wilson
authors.forename: S A
authors.initials: SA
authors.lastname: Grabczynska
authors.forename: B S
authors.initials: BS
authors.lastname: Carey
authors.forename: C M
authors.initials: CM
authors.lastname: Lewis
authors.forename: M A
authors.initials: MA
authors.lastname: Khamashta
authors.forename: G W
authors.initials: GW
authors.lastname: Duff
authors.forename: G R
authors.initials: GR
authors.lastname: Hughes
authors.forename: J L
authors.initials: JL
authors.lastname: Hawk
authors.forename: R W
authors.initials: RW
authors.lastname: Vaughan
authors.forename: J M
authors.initials: JM
authors.lastname: McGregor
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D019040:E-Selectin / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015810:Linkage Disequilibrium; D008178:Lupus Erythematosus, Cutaneous / Q000235:genetics*; D008179:Lupus Erythematosus, Discoid / Q000235:genetics; D016017:Odds Ratio; D010787:Photosensitivity Disorders / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011536:Prurigo / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D019040:E-Selectin; D007375:Interleukin-1; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10