Associations of ERAP1 coding variants and domain specific interaction with HLA-C∗06 in the early onset psoriasis patients of India

Associations of ERAP1 coding variants and domain specific interaction with HLA-C∗06 in the early onset psoriasis patients of India

Interferon-γ-induced aminopeptidase ERAP1 trims peptides within the endoplasmic reticulum so that they can be loaded onto MHC class I and presented to the CD8+ T-cells. ERAP1 association and its interaction with HLA-C∗06 is controversial across different populations. We have investigated the associa...

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Veröffentlicht in:Human immunology 2017-11, Vol.78 (11-12), p.724-730
Hauptverfasser: Das, Anamika, Chandra, Aditi, Chakraborty, Joyeeta, Chattopadhyay, Abhijit, Senapati, Swapan, Chatterjee, Gobinda, Chatterjee, Raghunath
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Sprache:eng
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Endoplasmic reticulum aminopeptidase 1
Epistasis
Generalized plaque type psoriasis
Human Leukocyte Antigen (HLA)-C∗06
Single nucleotide polymorphism
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container_end_page 730
container_issue 11-12
container_start_page 724
container_title Human immunology
container_volume 78
creator Das, Anamika
Chandra, Aditi
Chakraborty, Joyeeta
Chattopadhyay, Abhijit
Senapati, Swapan
Chatterjee, Gobinda
Chatterjee, Raghunath
description Interferon-γ-induced aminopeptidase ERAP1 trims peptides within the endoplasmic reticulum so that they can be loaded onto MHC class I and presented to the CD8+ T-cells. ERAP1 association and its interaction with HLA-C∗06 is controversial across different populations. We have investigated the association and possible functional role of non-synonymous SNPs at different exons of ERAP1 (rs26653: Arg127Pro, rs30187: Lys528Arg and rs27044: Gln730Glu) and their interactions with HLA-C∗06 in psoriasis. Significant associations of HLA-C∗06 (OR=5.47, P
doi_str_mv 10.1016/j.humimm.2017.08.006
format Article
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ERAP1 association and its interaction with HLA-C∗06 is controversial across different populations. We have investigated the association and possible functional role of non-synonymous SNPs at different exons of ERAP1 (rs26653: Arg127Pro, rs30187: Lys528Arg and rs27044: Gln730Glu) and their interactions with HLA-C∗06 in psoriasis. Significant associations of HLA-C∗06 (OR=5.47, P&lt;2.2×10−16), rs30187 (OR 1.35, P=7.4×10−4) and rs27044 (OR=1.24, P=5.8×10−3) were observed. All three ERAP1 SNPs showed significant association only for HLA-C∗06 positive patients, while rs30187 and rs27044 showed significant association only for early onset patients (rs30187: OR=1.47, P=9.6×10−5; rs27044: OR=1.36, P=3.3×10−4). No differential expression of ERAP1 was observed either between paired uninvolved and involved skin tissues of psoriasis patients or between non-risk and risk variants in the involved skin. Significant epistatic interaction was observed between HLA-C∗06 and the SNP (rs27044) located at the peptide-binding cavity of ERAP1. Evolutionary conservation analysis among mammals showed confinement of Lys528 and Gln730 within highly conserved regions of ERAP1 and suggested the possible detrimental effect of this allele in ERAP1 regulation.</description><identifier>ISSN: 0198-8859</identifier><identifier>EISSN: 1879-1166</identifier><identifier>DOI: 10.1016/j.humimm.2017.08.006</identifier><identifier>PMID: 28867178</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Endoplasmic reticulum aminopeptidase 1 ; Epistasis ; Generalized plaque type psoriasis ; Human Leukocyte Antigen (HLA)-C∗06 ; Single nucleotide polymorphism</subject><ispartof>Human immunology, 2017-11, Vol.78 (11-12), p.724-730</ispartof><rights>2017</rights><rights>Copyright © 2017. 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ERAP1 association and its interaction with HLA-C∗06 is controversial across different populations. We have investigated the association and possible functional role of non-synonymous SNPs at different exons of ERAP1 (rs26653: Arg127Pro, rs30187: Lys528Arg and rs27044: Gln730Glu) and their interactions with HLA-C∗06 in psoriasis. Significant associations of HLA-C∗06 (OR=5.47, P&lt;2.2×10−16), rs30187 (OR 1.35, P=7.4×10−4) and rs27044 (OR=1.24, P=5.8×10−3) were observed. All three ERAP1 SNPs showed significant association only for HLA-C∗06 positive patients, while rs30187 and rs27044 showed significant association only for early onset patients (rs30187: OR=1.47, P=9.6×10−5; rs27044: OR=1.36, P=3.3×10−4). No differential expression of ERAP1 was observed either between paired uninvolved and involved skin tissues of psoriasis patients or between non-risk and risk variants in the involved skin. Significant epistatic interaction was observed between HLA-C∗06 and the SNP (rs27044) located at the peptide-binding cavity of ERAP1. Evolutionary conservation analysis among mammals showed confinement of Lys528 and Gln730 within highly conserved regions of ERAP1 and suggested the possible detrimental effect of this allele in ERAP1 regulation.</description><subject>Endoplasmic reticulum aminopeptidase 1</subject><subject>Epistasis</subject><subject>Generalized plaque type psoriasis</subject><subject>Human Leukocyte Antigen (HLA)-C∗06</subject><subject>Single nucleotide polymorphism</subject><issn>0198-8859</issn><issn>1879-1166</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp9kMFuEzEURS1ERdPCHyDkJZuZ2jO2x7NBiqJCK0WiQrC2HPsNcZQZD35OUfcs-AP-r19SRyksWXnx7r1HPoS85azmjKurXb09jGEc64bxrma6Zky9IAuuu77iXKmXZMF4ryutZX9OLhB3jLGOdeIVOW-0Vh3v9IL8WiJGF2wOcUIaB3r9ZXnHqYs-TN_pvU3BThmpnTz1cbRhojiDC0NwNEwZknXHJv0Z8pberJfV6vH3H6bKjeYtULBp_0DLMmQ6YyxjGJDOhQbH1YK7nXywr8nZYPcIb57fS_Lt4_XX1U21_vzpdrVcV65VTa56rwYP3G5E2zopNTRKwkb1vbSi1SCEBCV409gN46KxugXBvR9kp1sLIIb2krw_7c4p_jgAZjMGdLDf2wniAQ3vWymK20aWqDhFXYqICQYzpzDa9GA4M0f_ZmdO_s3Rv2HaFP-l9u6ZcNiM4P-V_govgQ-nAJR_3gdIBl2R4cCHBC4bH8P_CU--4Zpk</recordid><startdate>201711</startdate><enddate>201711</enddate><creator>Das, Anamika</creator><creator>Chandra, Aditi</creator><creator>Chakraborty, Joyeeta</creator><creator>Chattopadhyay, Abhijit</creator><creator>Senapati, Swapan</creator><creator>Chatterjee, Gobinda</creator><creator>Chatterjee, Raghunath</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201711</creationdate><title>Associations of ERAP1 coding variants and domain specific interaction with HLA-C∗06 in the early onset psoriasis patients of India</title><author>Das, Anamika ; Chandra, Aditi ; Chakraborty, Joyeeta ; Chattopadhyay, Abhijit ; Senapati, Swapan ; Chatterjee, Gobinda ; Chatterjee, Raghunath</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-9d6fde1ab433c558e265eb6995a438e445e64122ab0142a83e41ddf5783aee4f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Endoplasmic reticulum aminopeptidase 1</topic><topic>Epistasis</topic><topic>Generalized plaque type psoriasis</topic><topic>Human Leukocyte Antigen (HLA)-C∗06</topic><topic>Single nucleotide polymorphism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Das, Anamika</creatorcontrib><creatorcontrib>Chandra, Aditi</creatorcontrib><creatorcontrib>Chakraborty, Joyeeta</creatorcontrib><creatorcontrib>Chattopadhyay, Abhijit</creatorcontrib><creatorcontrib>Senapati, Swapan</creatorcontrib><creatorcontrib>Chatterjee, Gobinda</creatorcontrib><creatorcontrib>Chatterjee, Raghunath</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Human immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Das, Anamika</au><au>Chandra, Aditi</au><au>Chakraborty, Joyeeta</au><au>Chattopadhyay, Abhijit</au><au>Senapati, Swapan</au><au>Chatterjee, Gobinda</au><au>Chatterjee, Raghunath</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Associations of ERAP1 coding variants and domain specific interaction with HLA-C∗06 in the early onset psoriasis patients of India</atitle><jtitle>Human immunology</jtitle><addtitle>Hum Immunol</addtitle><date>2017-11</date><risdate>2017</risdate><volume>78</volume><issue>11-12</issue><spage>724</spage><epage>730</epage><pages>724-730</pages><issn>0198-8859</issn><eissn>1879-1166</eissn><abstract>Interferon-γ-induced aminopeptidase ERAP1 trims peptides within the endoplasmic reticulum so that they can be loaded onto MHC class I and presented to the CD8+ T-cells. ERAP1 association and its interaction with HLA-C∗06 is controversial across different populations. We have investigated the association and possible functional role of non-synonymous SNPs at different exons of ERAP1 (rs26653: Arg127Pro, rs30187: Lys528Arg and rs27044: Gln730Glu) and their interactions with HLA-C∗06 in psoriasis. Significant associations of HLA-C∗06 (OR=5.47, P&lt;2.2×10−16), rs30187 (OR 1.35, P=7.4×10−4) and rs27044 (OR=1.24, P=5.8×10−3) were observed. All three ERAP1 SNPs showed significant association only for HLA-C∗06 positive patients, while rs30187 and rs27044 showed significant association only for early onset patients (rs30187: OR=1.47, P=9.6×10−5; rs27044: OR=1.36, P=3.3×10−4). No differential expression of ERAP1 was observed either between paired uninvolved and involved skin tissues of psoriasis patients or between non-risk and risk variants in the involved skin. Significant epistatic interaction was observed between HLA-C∗06 and the SNP (rs27044) located at the peptide-binding cavity of ERAP1. Evolutionary conservation analysis among mammals showed confinement of Lys528 and Gln730 within highly conserved regions of ERAP1 and suggested the possible detrimental effect of this allele in ERAP1 regulation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28867178</pmid><doi>10.1016/j.humimm.2017.08.006</doi><tpages>7</tpages></addata></record>
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subjects Endoplasmic reticulum aminopeptidase 1
Epistasis
Generalized plaque type psoriasis
Human Leukocyte Antigen (HLA)-C∗06
Single nucleotide polymorphism
title Associations of ERAP1 coding variants and domain specific interaction with HLA-C∗06 in the early onset psoriasis patients of India
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