Long noncoding RNA polymorphisms influence susceptibility to endemic pemphigus foliaceus

Summary Background Pemphigus foliaceus (PF) is an epidermal autoimmune disease, characterized by the presence of autoantibodies against the desmosomal protein desmoglein 1. Genetic and environmental factors contribute to PF, a complex disease that is endemic in Brazil and Colombia and neighbouring countries, and in Tunisia. Long noncoding RNAs (lncRNAs) may participate in gene regulation by interacting with DNA, proteins and other RNAs. Dysregulation of lncRNAs has recently been recognized as an important coplayer in the onset or progression of complex diseases. In addition, single‐nucleotide polymorphisms (SNPs) located in lncRNA genes have been associated with differential risk to cancer, autoimmunity and infection. Objectives Here, we aimed to investigate whether SNPs in lncRNA genes are associated with differential susceptibility to endemic PF. Materials and methods We integrated data from the lncRNA SNP database with genome‐wide genotype data obtained for 229 patients and 6681 controls. We tested the association between endemic PF and 2080 SNPs located in lncRNAs applying logistic regression. Results The most significantly associated SNP was rs7144332 (OR = 1·63, P = 2·8 × 10–6), located in the lncRNA gene AL110292·1. Results for five other SNPs were suggestive of association (P < 0·001). In silico analysis indicated that five of the six SNPs impact transcription, three may influence lncRNA's secondary structure, and three may alter microRNA–lncRNA interactions. Conclusions We showed, for the first time, that variation in lncRNA genes may influence pemphigus pathogenesis. Our findings highlight the importance of lncRNA variation in autoimmune and possibly other complex diseases and suggest polymorphisms for functional validation. What's already known about this topic? The multifactorial autoimmune blistering skin disease pemphigus foliaceus (PF) presents a genetic susceptibility component that is not fully understood. Although PF is rare worldwide, it reaches a prevalence of 1·5–3% in some regions of Brazil, the highest ever reported for an autoimmune disease. Long noncoding RNA (lncRNA) polymorphisms have been associated with some complex diseases but have not yet been studied in any form of pemphigus. What does this study add? Genetic variation of lncRNA may influence susceptibility to PF via its effect on lncRNA structure, on transcription of nearby genes, and on microRNA–lncRNA interactions. We have shown, for the first time, that variation in lnc