Genetic variability of immune‐related lncRNAs: polymorphisms in LINC‐PINT and LY86‐AS1 are associated with pemphigus foliaceus susceptibility
Pemphigus foliaceus (PF) is an autoimmune blistering disease of the skin, clinically characterized by erosions and, histopathologically, by acantholysis. PF is endemic in the Brazilian Central‐Western region. Numerous single nucleotide polymorphisms (SNPs) have been shown to affect the susceptibilit...
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| Veröffentlicht in: | Experimental dermatology 2021-06, Vol.30 (6), p.831-840 |
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| creator | Salviano‐Silva, Amanda Farias, Ticiana Della Justina Bumiller‐Bini, Valéria Castro, Mariana de Sousa Lobo‐Alves, Sara Cristina Busch, Hauke Pföhler, Claudia Worm, Margitta Goebeler, Matthias Beek, Nina Franke, Andre Wittig, Michael Zillikens, Detlef Almeida, Rodrigo Coutinho Hundt, Jennifer Elisabeth Boldt, Angelica Beate Winter Ibrahim, Saleh Augusto, Danillo Gardenal Petzl‐Erler, Maria Luiza Schmidt, Enno Malheiros, Danielle |
| description | Pemphigus foliaceus (PF) is an autoimmune blistering disease of the skin, clinically characterized by erosions and, histopathologically, by acantholysis. PF is endemic in the Brazilian Central‐Western region. Numerous single nucleotide polymorphisms (SNPs) have been shown to affect the susceptibility for PF, including SNPs at long non‐coding RNA (lncRNA) genes, which are known to participate in many physiological and pathogenic processes, such as autoimmunity. Here, we investigated whether the genetic variation of immune‐related lncRNA genes affects the risk for endemic and sporadic forms of PF. We analysed 692 novel SNPs for PF from 135 immune‐related lncRNA genes in 227 endemic PF patients and 194 controls. The SNPs were genotyped by Illumina microarray and analysed by applying logistic regression at additive model, with correction for sex and population structure. Six associated SNPs were also evaluated in an independent German cohort of 76 sporadic PF patients and 150 controls. Further, we measured the expression levels of two associated lncRNA genes (LINC‐PINT and LY86‐AS1) by quantitative PCR, stratified by genotypes, in peripheral blood mononuclear cells of healthy subjects. We found 27 SNPs in 11 lncRNA genes associated with endemic PF (p |
| doi_str_mv | 10.1111/exd.14275 |
| format | Article |
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PF is endemic in the Brazilian Central‐Western region. Numerous single nucleotide polymorphisms (SNPs) have been shown to affect the susceptibility for PF, including SNPs at long non‐coding RNA (lncRNA) genes, which are known to participate in many physiological and pathogenic processes, such as autoimmunity. Here, we investigated whether the genetic variation of immune‐related lncRNA genes affects the risk for endemic and sporadic forms of PF. We analysed 692 novel SNPs for PF from 135 immune‐related lncRNA genes in 227 endemic PF patients and 194 controls. The SNPs were genotyped by Illumina microarray and analysed by applying logistic regression at additive model, with correction for sex and population structure. Six associated SNPs were also evaluated in an independent German cohort of 76 sporadic PF patients and 150 controls. Further, we measured the expression levels of two associated lncRNA genes (LINC‐PINT and LY86‐AS1) by quantitative PCR, stratified by genotypes, in peripheral blood mononuclear cells of healthy subjects. We found 27 SNPs in 11 lncRNA genes associated with endemic PF (p < .05 without overlapping with protein‐coding genes). Among them, the LINC‐PINT SNP rs10228040*A (OR = 1.47, p = .012) was also associated with increased susceptibility for sporadic PF (OR = 2.28, p = .002). Moreover, the A+ carriers of LY86‐AS1*rs12192707 mark lowest LY86‐AS1 RNA levels, which might be associated with a decreasing autoimmune response. Our results suggest a critical role of lncRNA variants in immunopathogenesis of both PF endemic and sporadic forms.</description><identifier>ISSN: 0906-6705</identifier><identifier>EISSN: 1600-0625</identifier><identifier>DOI: 10.1111/exd.14275</identifier><identifier>PMID: 33394553</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>association study ; Autoimmunity ; Genetic variability ; Immunopathogenesis ; Leukocytes (mononuclear) ; LINC‐PINT ; lncRNAs ; LY86‐AS1 ; Non-coding RNA ; Pemphigus ; pemphigus foliaceus ; Peripheral blood mononuclear cells ; Population structure ; Single-nucleotide polymorphism ; Skin diseases</subject><ispartof>Experimental dermatology, 2021-06, Vol.30 (6), p.831-840</ispartof><rights>2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3535-6b3d95c4bd49ffeec911f1cebb20d8d289019297386cb1fb1d1ed92c32a53fb73</citedby><cites>FETCH-LOGICAL-c3535-6b3d95c4bd49ffeec911f1cebb20d8d289019297386cb1fb1d1ed92c32a53fb73</cites><orcidid>0000-0002-0902-9622 ; 0000-0002-5668-307X ; 0000-0001-7834-8128 ; 0000-0003-2741-7028 ; 0000-0001-7966-056X ; 0000-0002-0345-5276 ; 0000-0002-1462-4426 ; 0000-0003-4763-4521 ; 0000-0002-3449-1245 ; 0000-0002-2528-9707 ; 0000-0003-4000-2417 ; 0000-0003-0384-114X ; 0000-0001-5665-8547 ; 0000-0002-3606-2428 ; 0000-0001-7827-2290 ; 0000-0002-1206-8913</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fexd.14275$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fexd.14275$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33394553$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Salviano‐Silva, Amanda</creatorcontrib><creatorcontrib>Farias, Ticiana Della Justina</creatorcontrib><creatorcontrib>Bumiller‐Bini, Valéria</creatorcontrib><creatorcontrib>Castro, Mariana de Sousa</creatorcontrib><creatorcontrib>Lobo‐Alves, Sara Cristina</creatorcontrib><creatorcontrib>Busch, Hauke</creatorcontrib><creatorcontrib>Pföhler, Claudia</creatorcontrib><creatorcontrib>Worm, Margitta</creatorcontrib><creatorcontrib>Goebeler, Matthias</creatorcontrib><creatorcontrib>Beek, Nina</creatorcontrib><creatorcontrib>Franke, Andre</creatorcontrib><creatorcontrib>Wittig, Michael</creatorcontrib><creatorcontrib>Zillikens, Detlef</creatorcontrib><creatorcontrib>Almeida, Rodrigo Coutinho</creatorcontrib><creatorcontrib>Hundt, Jennifer Elisabeth</creatorcontrib><creatorcontrib>Boldt, Angelica Beate Winter</creatorcontrib><creatorcontrib>Ibrahim, Saleh</creatorcontrib><creatorcontrib>Augusto, Danillo Gardenal</creatorcontrib><creatorcontrib>Petzl‐Erler, Maria Luiza</creatorcontrib><creatorcontrib>Schmidt, Enno</creatorcontrib><creatorcontrib>Malheiros, Danielle</creatorcontrib><title>Genetic variability of immune‐related lncRNAs: polymorphisms in LINC‐PINT and LY86‐AS1 are associated with pemphigus foliaceus susceptibility</title><title>Experimental dermatology</title><addtitle>Exp Dermatol</addtitle><description>Pemphigus foliaceus (PF) is an autoimmune blistering disease of the skin, clinically characterized by erosions and, histopathologically, by acantholysis. PF is endemic in the Brazilian Central‐Western region. Numerous single nucleotide polymorphisms (SNPs) have been shown to affect the susceptibility for PF, including SNPs at long non‐coding RNA (lncRNA) genes, which are known to participate in many physiological and pathogenic processes, such as autoimmunity. Here, we investigated whether the genetic variation of immune‐related lncRNA genes affects the risk for endemic and sporadic forms of PF. We analysed 692 novel SNPs for PF from 135 immune‐related lncRNA genes in 227 endemic PF patients and 194 controls. The SNPs were genotyped by Illumina microarray and analysed by applying logistic regression at additive model, with correction for sex and population structure. Six associated SNPs were also evaluated in an independent German cohort of 76 sporadic PF patients and 150 controls. Further, we measured the expression levels of two associated lncRNA genes (LINC‐PINT and LY86‐AS1) by quantitative PCR, stratified by genotypes, in peripheral blood mononuclear cells of healthy subjects. We found 27 SNPs in 11 lncRNA genes associated with endemic PF (p < .05 without overlapping with protein‐coding genes). Among them, the LINC‐PINT SNP rs10228040*A (OR = 1.47, p = .012) was also associated with increased susceptibility for sporadic PF (OR = 2.28, p = .002). Moreover, the A+ carriers of LY86‐AS1*rs12192707 mark lowest LY86‐AS1 RNA levels, which might be associated with a decreasing autoimmune response. Our results suggest a critical role of lncRNA variants in immunopathogenesis of both PF endemic and sporadic forms.</description><subject>association study</subject><subject>Autoimmunity</subject><subject>Genetic variability</subject><subject>Immunopathogenesis</subject><subject>Leukocytes (mononuclear)</subject><subject>LINC‐PINT</subject><subject>lncRNAs</subject><subject>LY86‐AS1</subject><subject>Non-coding RNA</subject><subject>Pemphigus</subject><subject>pemphigus foliaceus</subject><subject>Peripheral blood mononuclear cells</subject><subject>Population structure</subject><subject>Single-nucleotide polymorphism</subject><subject>Skin diseases</subject><issn>0906-6705</issn><issn>1600-0625</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp1kc1u1DAURi0EotPCghdAltjAIq1_4mTMbjSUMtJoQFAkWFmOfU1dJXFqJ7Sz4xGQeEOeBNMUFkjcja-l4-NP-hB6QskxzXMCN_aYlqwW99CCVoQUpGLiPloQSaqiqok4QIcpXRJCa16Lh-iAcy5LIfgC_TiDHkZv8FcdvW5868c9Dg77rpt6-Pnte4RWj2Bx25v3u1V6iYfQ7rsQhwufuoR9j7eb3TqD7za7c6x7i7efl1W-rz5QrCNgnVIw_tZx7ccLPECX336ZEnah9dpA3tKUDAyjn_9_hB443SZ4fHceoY-vT8_Xb4rt27PNerUtDBdcFFXDrRSmbGwpnQMwklJHDTQNI3Zp2VISKpms-bIyDXUNtRSsZIYzLbhran6Ens_eIYarCdKoOp9ztK3uIUxJsbIWRFakZhl99g96GabY53SKiZJSQQSnmXoxUyaGlCI4NUTf6bhXlKjfTanclLptKrNP74xT04H9S_6pJgMnM3DtW9j_36ROP72alb8AGG-hOA</recordid><startdate>202106</startdate><enddate>202106</enddate><creator>Salviano‐Silva, Amanda</creator><creator>Farias, Ticiana Della Justina</creator><creator>Bumiller‐Bini, Valéria</creator><creator>Castro, Mariana de Sousa</creator><creator>Lobo‐Alves, Sara Cristina</creator><creator>Busch, Hauke</creator><creator>Pföhler, Claudia</creator><creator>Worm, Margitta</creator><creator>Goebeler, Matthias</creator><creator>Beek, Nina</creator><creator>Franke, Andre</creator><creator>Wittig, Michael</creator><creator>Zillikens, Detlef</creator><creator>Almeida, Rodrigo Coutinho</creator><creator>Hundt, Jennifer Elisabeth</creator><creator>Boldt, Angelica Beate Winter</creator><creator>Ibrahim, Saleh</creator><creator>Augusto, Danillo Gardenal</creator><creator>Petzl‐Erler, Maria Luiza</creator><creator>Schmidt, Enno</creator><creator>Malheiros, Danielle</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0902-9622</orcidid><orcidid>https://orcid.org/0000-0002-5668-307X</orcidid><orcidid>https://orcid.org/0000-0001-7834-8128</orcidid><orcidid>https://orcid.org/0000-0003-2741-7028</orcidid><orcidid>https://orcid.org/0000-0001-7966-056X</orcidid><orcidid>https://orcid.org/0000-0002-0345-5276</orcidid><orcidid>https://orcid.org/0000-0002-1462-4426</orcidid><orcidid>https://orcid.org/0000-0003-4763-4521</orcidid><orcidid>https://orcid.org/0000-0002-3449-1245</orcidid><orcidid>https://orcid.org/0000-0002-2528-9707</orcidid><orcidid>https://orcid.org/0000-0003-4000-2417</orcidid><orcidid>https://orcid.org/0000-0003-0384-114X</orcidid><orcidid>https://orcid.org/0000-0001-5665-8547</orcidid><orcidid>https://orcid.org/0000-0002-3606-2428</orcidid><orcidid>https://orcid.org/0000-0001-7827-2290</orcidid><orcidid>https://orcid.org/0000-0002-1206-8913</orcidid></search><sort><creationdate>202106</creationdate><title>Genetic variability of immune‐related lncRNAs: polymorphisms in LINC‐PINT and LY86‐AS1 are associated with pemphigus foliaceus susceptibility</title><author>Salviano‐Silva, Amanda ; Farias, Ticiana Della Justina ; Bumiller‐Bini, Valéria ; Castro, Mariana de Sousa ; Lobo‐Alves, Sara Cristina ; Busch, Hauke ; Pföhler, Claudia ; Worm, Margitta ; Goebeler, Matthias ; Beek, Nina ; Franke, Andre ; Wittig, Michael ; Zillikens, Detlef ; Almeida, Rodrigo Coutinho ; Hundt, Jennifer Elisabeth ; Boldt, Angelica Beate Winter ; Ibrahim, Saleh ; Augusto, Danillo Gardenal ; Petzl‐Erler, Maria Luiza ; Schmidt, Enno ; Malheiros, Danielle</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3535-6b3d95c4bd49ffeec911f1cebb20d8d289019297386cb1fb1d1ed92c32a53fb73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>association study</topic><topic>Autoimmunity</topic><topic>Genetic variability</topic><topic>Immunopathogenesis</topic><topic>Leukocytes (mononuclear)</topic><topic>LINC‐PINT</topic><topic>lncRNAs</topic><topic>LY86‐AS1</topic><topic>Non-coding RNA</topic><topic>Pemphigus</topic><topic>pemphigus foliaceus</topic><topic>Peripheral blood mononuclear cells</topic><topic>Population structure</topic><topic>Single-nucleotide polymorphism</topic><topic>Skin diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Salviano‐Silva, Amanda</creatorcontrib><creatorcontrib>Farias, Ticiana Della Justina</creatorcontrib><creatorcontrib>Bumiller‐Bini, Valéria</creatorcontrib><creatorcontrib>Castro, Mariana de Sousa</creatorcontrib><creatorcontrib>Lobo‐Alves, Sara Cristina</creatorcontrib><creatorcontrib>Busch, Hauke</creatorcontrib><creatorcontrib>Pföhler, Claudia</creatorcontrib><creatorcontrib>Worm, Margitta</creatorcontrib><creatorcontrib>Goebeler, Matthias</creatorcontrib><creatorcontrib>Beek, Nina</creatorcontrib><creatorcontrib>Franke, Andre</creatorcontrib><creatorcontrib>Wittig, Michael</creatorcontrib><creatorcontrib>Zillikens, Detlef</creatorcontrib><creatorcontrib>Almeida, Rodrigo Coutinho</creatorcontrib><creatorcontrib>Hundt, Jennifer Elisabeth</creatorcontrib><creatorcontrib>Boldt, Angelica Beate Winter</creatorcontrib><creatorcontrib>Ibrahim, Saleh</creatorcontrib><creatorcontrib>Augusto, Danillo Gardenal</creatorcontrib><creatorcontrib>Petzl‐Erler, Maria Luiza</creatorcontrib><creatorcontrib>Schmidt, Enno</creatorcontrib><creatorcontrib>Malheiros, Danielle</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental dermatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Salviano‐Silva, Amanda</au><au>Farias, Ticiana Della Justina</au><au>Bumiller‐Bini, Valéria</au><au>Castro, Mariana de Sousa</au><au>Lobo‐Alves, Sara Cristina</au><au>Busch, Hauke</au><au>Pföhler, Claudia</au><au>Worm, Margitta</au><au>Goebeler, Matthias</au><au>Beek, Nina</au><au>Franke, Andre</au><au>Wittig, Michael</au><au>Zillikens, Detlef</au><au>Almeida, Rodrigo Coutinho</au><au>Hundt, Jennifer Elisabeth</au><au>Boldt, Angelica Beate Winter</au><au>Ibrahim, Saleh</au><au>Augusto, Danillo Gardenal</au><au>Petzl‐Erler, Maria Luiza</au><au>Schmidt, Enno</au><au>Malheiros, Danielle</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic variability of immune‐related lncRNAs: polymorphisms in LINC‐PINT and LY86‐AS1 are associated with pemphigus foliaceus susceptibility</atitle><jtitle>Experimental dermatology</jtitle><addtitle>Exp Dermatol</addtitle><date>2021-06</date><risdate>2021</risdate><volume>30</volume><issue>6</issue><spage>831</spage><epage>840</epage><pages>831-840</pages><issn>0906-6705</issn><eissn>1600-0625</eissn><abstract>Pemphigus foliaceus (PF) is an autoimmune blistering disease of the skin, clinically characterized by erosions and, histopathologically, by acantholysis. PF is endemic in the Brazilian Central‐Western region. Numerous single nucleotide polymorphisms (SNPs) have been shown to affect the susceptibility for PF, including SNPs at long non‐coding RNA (lncRNA) genes, which are known to participate in many physiological and pathogenic processes, such as autoimmunity. Here, we investigated whether the genetic variation of immune‐related lncRNA genes affects the risk for endemic and sporadic forms of PF. We analysed 692 novel SNPs for PF from 135 immune‐related lncRNA genes in 227 endemic PF patients and 194 controls. The SNPs were genotyped by Illumina microarray and analysed by applying logistic regression at additive model, with correction for sex and population structure. Six associated SNPs were also evaluated in an independent German cohort of 76 sporadic PF patients and 150 controls. Further, we measured the expression levels of two associated lncRNA genes (LINC‐PINT and LY86‐AS1) by quantitative PCR, stratified by genotypes, in peripheral blood mononuclear cells of healthy subjects. We found 27 SNPs in 11 lncRNA genes associated with endemic PF (p < .05 without overlapping with protein‐coding genes). Among them, the LINC‐PINT SNP rs10228040*A (OR = 1.47, p = .012) was also associated with increased susceptibility for sporadic PF (OR = 2.28, p = .002). Moreover, the A+ carriers of LY86‐AS1*rs12192707 mark lowest LY86‐AS1 RNA levels, which might be associated with a decreasing autoimmune response. Our results suggest a critical role of lncRNA variants in immunopathogenesis of both PF endemic and sporadic forms.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33394553</pmid><doi>10.1111/exd.14275</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-0902-9622</orcidid><orcidid>https://orcid.org/0000-0002-5668-307X</orcidid><orcidid>https://orcid.org/0000-0001-7834-8128</orcidid><orcidid>https://orcid.org/0000-0003-2741-7028</orcidid><orcidid>https://orcid.org/0000-0001-7966-056X</orcidid><orcidid>https://orcid.org/0000-0002-0345-5276</orcidid><orcidid>https://orcid.org/0000-0002-1462-4426</orcidid><orcidid>https://orcid.org/0000-0003-4763-4521</orcidid><orcidid>https://orcid.org/0000-0002-3449-1245</orcidid><orcidid>https://orcid.org/0000-0002-2528-9707</orcidid><orcidid>https://orcid.org/0000-0003-4000-2417</orcidid><orcidid>https://orcid.org/0000-0003-0384-114X</orcidid><orcidid>https://orcid.org/0000-0001-5665-8547</orcidid><orcidid>https://orcid.org/0000-0002-3606-2428</orcidid><orcidid>https://orcid.org/0000-0001-7827-2290</orcidid><orcidid>https://orcid.org/0000-0002-1206-8913</orcidid></addata></record> |
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| ispartof | Experimental dermatology, 2021-06, Vol.30 (6), p.831-840 |
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| language | eng |
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| source | Wiley Online Library Journals |
| subjects | association study Autoimmunity Genetic variability Immunopathogenesis Leukocytes (mononuclear) LINC‐PINT lncRNAs LY86‐AS1 Non-coding RNA Pemphigus pemphigus foliaceus Peripheral blood mononuclear cells Population structure Single-nucleotide polymorphism Skin diseases |
| title | Genetic variability of immune‐related lncRNAs: polymorphisms in LINC‐PINT and LY86‐AS1 are associated with pemphigus foliaceus susceptibility |
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