A 3′UTR polymorphism marks differential KLRG1 mRNA levels through disruption of a miR-584-5p binding site and associates with pemphigus foliaceus susceptibility

Cipolla, Gabriel Adelman; Park, Jong Kook; Oliveira, Liana Alves de; Lobo‐Alves, Sara Cristina; Almeida, Rodrigo Coutinho de; Farias, Ticiana Della Justina; Lemos, Débora de Souza; Malheiros, Danielle; Lavker, Robert M.; Petzl-Erler, María Luiza

doi:10.1016/j.bbagrm.2016.07.006

Cited by 28 publications

(31 citation statements)

References 49 publications

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“…Polymorphisms in other proteincoding genes have been found associated with EPF [7][8][9][10][11][12][13][14] . A recent study showed that a 3' untranslated region polymorphism is associated with susceptibility to EPF by affecting a microRNA (miRNA) binding site 15 . Despite that, polymorphisms in non-coding regions have not been systematically analysed in any form of pemphigus.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA polymorphisms influence susceptibility to endemic pemphigus foliaceus

et al. 2019

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What is already known about this topic?  The multifactorial autoimmune blistering skin disease pemphigus foliaceus presents a genetic susceptibility component that is not fully understood.  Although pemphigus foliaceus is rare worldwide, it reaches the prevalence of 1.5% to 3% in some regions of Brazil, the highest ever reported for an autoimmune disease.  LncRNA polymorphisms have been associated with some complex diseases but were not yet studied in any form of pemphigus. What does this study add?  Genetic variation of lncRNA may influence susceptibility to pemphigus foliaceus via its effect on lncRNA structure, on transcription of nearby genes, and on microRNA-lncRNA interactions.

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Section: Introductionmentioning

confidence: 99%

Long noncoding RNA polymorphisms influence susceptibility to endemic pemphigus foliaceus

et al. 2019

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“…Two‐hundred and twenty‐nine unrelated patients with a PF diagnosis based on clinical, histopathological and/or immunohistochemical criteria were recruited at hospitals from endemic areas as described in Cipolla et al . The control sample encompassed 194 unrelated individuals with no known history of autoimmune diseases who lived in endemic areas.…”

Section: Methodsmentioning

confidence: 99%

“…The first genetic associations reported were variants within the human leucocyte antigen ( HLA ) genes, with strong associations with alleles of HLA‐DRB1 and HLA‐DQB1 . Furthermore, our group has demonstrated several other associations of PF with genes involved in immune responses …”

Section: Introductionmentioning

confidence: 91%

Screening the full leucocyte receptor complex genomic region revealed associations with pemphigus that might be explained by gene regulation

et al. 2018

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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 SNPs were analysed in 229 patients with PF and 194 controls. Three SNPs 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 VSTM1, LILRB1/2, LAIR1/2, LILRA3/4 and LENG8. The rs35336528 (OR = 3·44; P = 0·009) and rs1865097 (OR = 0·57; P = 0·005) SNPs in LENG8 and FCAR genes, respectively, were also associated with PF. Moreover, we found four haplotypes with SNPs within the KIR3DL2/3, LAIR2 and LILRB1 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.

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“…Although the epidemiological data imply an environmental aetiology for FS, only some residents of the endemic regions develop the disease, because host factors play an important role in determining whether an exposed person will develop the disease. Association studies between FS and immune‐related genes demonstrated that alleles of HLA‐DR and ‐DQ, CIITA, IL6, CD40, CD40LG, BAFF, KIR genes and their HLA ligands, LAIR1 and LAIR2 , and KLRG1 are important factors modulating disease pathogenesis (Augusto, Lobo‐Alves, Melo, Pereira, & Petzl‐Erler, ; Augusto et al., ; Camargo, Augusto, & Petzl‐Erler, ; Cipolla et al., ; Malheiros & Petzl‐Erler, ; Pavoni, Roxo, Marquart Filho, & Petzl‐Erler, ; Pereira et al., ; Petzl‐Erler & Santamaria, ; Piovezan & Petzl‐Erler, ). Yet, the epidemiology and the familial distribution of the disease indicate that still other genes may contribute to its pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Region 1p13.2 including the RSBN1, PTPN22, AP4B1 and long non‐coding RNA genes does not bear risk factors for endemic pemphigus foliaceus (fogo selvagem)

Lobo‐Alves

Oliveira

Petzl‐Erler

2019

Int J Immunogenetics

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Pemphigus foliaceus (PF) is an autoimmune skin disease characterized by autoantibodies directed mainly against desmoglein‐1. The purpose of this study was to determine whether differential susceptibility to endemic PF in Brazil (fogo selvagem) is associated with polymorphisms at the cytogenetic location 1p13.2. Four single nucleotide polymorphisms that together tag 28 SNPs on a segment of approximately 312,000 bp encompassing the protein‐coding genes MAGI3, PHTF1, RSBN1, PTPN22, BCL2L15, AP4B1, DCLRE1B, the pseudogenes MTND5P20, RPS2P14 (AL133517.1) and the long non‐coding RNA genes AL137856.1, and AP4B1‐AS1 were used as markers for association analysis in a case–control study. Allele, genotype and haplotype frequencies of rs33996649, rs2476601, rs3789604 and rs3195954 were compared between patient and control samples. No significant association was found. Lack of association with rs2476601 of the PTPN22 gene agrees with previous results for pemphigus vulgaris and the Tunisian form of endemic pemphigus foliaceus. The other three SNPs had never been analysed before in any form of pemphigus. We conclude that variants in structural and regulatory sites of region 1p13.2 are not susceptibility factors for fogo selvagem. We suggest careful investigation of this genomic region in diseases that had been previously associated with PTPN22, since there are several other genes relevant for immune‐mediated diseases located in 1p13.2.

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A 3′UTR polymorphism marks differential KLRG1 mRNA levels through disruption of a miR-584-5p binding site and associates with pemphigus foliaceus susceptibility

Abstract: Genetic variations mapping to 3' untranslated regions

Cited by 28 publications

References 49 publications

Long noncoding RNA polymorphisms influence susceptibility to endemic pemphigus foliaceus

Long noncoding RNA polymorphisms influence susceptibility to endemic pemphigus foliaceus

Screening the full leucocyte receptor complex genomic region revealed associations with pemphigus that might be explained by gene regulation

Region 1p13.2 including the RSBN1, PTPN22, AP4B1 and long non‐coding RNA genes does not bear risk factors for endemic pemphigus foliaceus (fogo selvagem)

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