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.
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.
Authors: Elena Sanchez; Ajay Nadig; Bruce C Richardson; Barry I Freedman; Kenneth M Kaufman; Jennifer A Kelly; Timothy B Niewold; Diane L Kamen; Gary S Gilkeson; Julie T Ziegler; Carl D Langefeld; Graciela S Alarcón; Jeffrey C Edberg; Rosalind Ramsey-Goldman; Michelle Petri; Elizabeth E Brown; Robert P Kimberly; John D Reveille; Luis M Vilá; Joan T Merrill; Juan-Manuel Anaya; Judith A James; Bernardo A Pons-Estel; Javier Martin; So-Yeon Park; So-Young Bang; Sang-Cheol Bae; Kathy L Moser; Timothy J Vyse; Lindsey A Criswell; Patrick M Gaffney; Betty P Tsao; Chaim O Jacob; John B Harley; Marta E Alarcón-Riquelme; Amr H Sawalha Journal: Ann Rheum Dis Date: 2011-06-30 Impact factor: 19.103
Authors: Gulnara Mamyrova; Terrance P O'Hanlon; Laura Sillers; Karen Malley; Laura James-Newton; Christina G Parks; Glinda S Cooper; Janardan P Pandey; Frederick W Miller; Lisa G Rider Journal: Arthritis Rheum Date: 2008-12
Authors: Tiina M Järvinen; Anna Hellquist; Sari Koskenmies; Elisabet Einarsdottir; Jaana Panelius; Taina Hasan; Heikki Julkunen; Leonid Padyukov; Marika Kvarnström; Marie Wahren-Herlenius; Filippa Nyberg; Mauro D'Amato; Juha Kere; Ulpu Saarialho-Kere Journal: PLoS One Date: 2010-12-02 Impact factor: 3.240
Authors: N Schweintzger; A Gruber-Wackernagel; E Reginato; I Bambach; F Quehenberger; S N Byrne; P Wolf Journal: Br J Dermatol Date: 2015-07-30 Impact factor: 9.302