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 photosens itivity disorder, which may predispose to several related but distinct cond itions, including subacute cutaneous lupus erythematosus (SCLE), discoid lu pus erythematosus (DLE) and actinic prurigo (AP). Objectives To examine specific candidate genes for shared susceptibility al leles between these related phenotypes. Methods Eighty-five caucasian patients with annular SCLE or DLE were recrui ted, in addition to 102 first-degree relatives. The prevalence of PLE in bo th the patient and relative groups was determined by detailed interview and clinical examination. Eighty-five patients with pure PLE and 59 patients w ith AP were also recruited. Candidate genes were analysed by typing of sing le nucleotide polymorphisms of ILIO (-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 CIT), IL1RN (+ 2018 T/C) and TNF (-308 G/A) using polym erase chain reaction (PCR) with sequence-specific primers and 5'-nuclease P CR. 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 s trong linkage disequilibrium between TNF - 308 A and the HLA A*01, B*08, DR B1*0301 haplotype. A negative association was also found between SCLE and t he IL1B + 3954 T allele (P = 0.039), but the significance was lost on corre ction 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 wit h a number of autoimmune conditions. Although many of the other loci that w e chose failed to demonstrate an association, a candidate gene approach rem ains the most logical one, and the most likely to yield positive results in the future.