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Screening the full leucocyte receptor complex genomic region revealed associations with pemphigus that might be explained by gene regulation
Author(s) -
Farias Ticiana Della Justina,
Augusto Danillo G.,
Almeida Rodrigo Coutinho,
Malheiros Danielle,
PetzlErler Maria Luiza
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13003
Subject(s) - single nucleotide polymorphism , haplotype , biology , genetics , gene , pemphigus foliaceus , snp , autoantibody , immunology , genotype , antibody
Summary Pemphigus foliaceus ( PF ) is a blistering autoimmune skin disease rare in most of the world but endemic in certain regions of Brazil. PF is characterized by the detachment of epidermal cells and the presence of autoantibodies against desmoglein 1. In previous studies, we have shown that genetic polymorphisms and variable expression levels of certain leucocyte receptor complex ( LRC ) genes were associated with PF . However, the role of the LRC on PF susceptibility remained to be investigated. Here, we analysed 527 tag single nucleotide polymorphisms ( SNPs ) distributed within the 1·5 Mb LRC . After quality control, a total of 176 SNP s were analysed in 229 patients with PF and 194 controls. Three SNP s were associated with differential susceptibility to PF . The intergenic variant rs465169 [odds ratio ( OR) = 1·50; P = 0·004] is located in a region that might regulate several immune‐related genes, including VSTM 1 , LILRB 1/2 , LAIR 1/2 , LILRA 3/4 and LENG 8 . The rs35336528 ( OR = 3·44; P = 0·009) and rs1865097 ( OR = 0·57; P = 0·005) SNP s in LENG 8 and FCAR genes, respectively, were also associated with PF . Moreover, we found four haplotypes with SNP s within the KIR 3 DL 2/3 , LAIR 2 and LILRB 1 genes associated with PF ( P < 0·05), which corroborate previously reported associations. Thus, our results confirm the importance of the LRC for differential susceptibility to PF and reveal new markers that might influence expression levels of several LRC genes, as well as candidates for further functional studies.