A candidate gene analysis of three related photosensitivity disorders: Cutaneous lupus erythematosus, polymorphic light eruption and actinic prurigo

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). Objectives: 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.