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Article: Nasopharyngeal carcinoma MHC region deep sequencing identifies HLA and novel non-HLA TRIM31 and TRIM39 loci

TitleNasopharyngeal carcinoma MHC region deep sequencing identifies HLA and novel non-HLA TRIM31 and TRIM39 loci
Authors
Issue Date2020
PublisherNature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/commsbio
Citation
Communications Biology, 2020, v. 3, p. article no. 759 How to Cite?
AbstractDespite pronounced associations of major histocompatibility complex (MHC) regions with nasopharyngeal carcinoma (NPC), causal variants underlying NPC pathogenesis remain elusive. Our large-scale comprehensive MHC region deep sequencing study of 5689 Hong Kong Chinese identifies eight independent NPC-associated signals and provides mechanistic insight for disrupted transcription factor binding, altering target gene transcription. Two novel protective variants, rs2517664 (Trs2517664 = 4.6%, P = 6.38 × 10−21) and rs117495548 (Grs117495548 = 3.0%, P = 4.53 × 10−13), map near TRIM31 and TRIM39/TRIM39-RPP21; multiple independent protective signals map near HLA-B including a previously unreported variant, rs2523589 (P = 1.77 × 10−36). The rare HLA-B*07:05 allele (OR < 0.015, P = 5.83 × 10−21) is absent in NPC, but present in controls. The most prevalent haplotype lacks seven independent protective alleles (OR = 1.56) and the one with additional Asian-specific susceptibility rs9391681 allele (OR = 2.66) significantly increased NPC risk. Importantly, this study provides new evidence implicating two non-human leukocyte antigen (HLA) genes, E3 ubiquitin ligases, TRIM31 and TRIM39, impacting innate immune responses, with NPC risk reduction, independent of classical HLA class I/II alleles.
Persistent Identifierhttp://hdl.handle.net/10722/295469
ISSN
2020 SCImago Journal Rankings: 2.812
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNing, L-
dc.contributor.authorKo, JMY-
dc.contributor.authorYu, VZ-
dc.contributor.authorNg, HY-
dc.contributor.authorChan, CKC-
dc.contributor.authorTao, L-
dc.contributor.authorLam, SY-
dc.contributor.authorLeong, MML-
dc.contributor.authorNgan, RKC-
dc.contributor.authorKwong, DLW-
dc.contributor.authorLee, AWM-
dc.contributor.authorNg, WT-
dc.contributor.authorCheng, A-
dc.contributor.authorTung, S-
dc.contributor.authorLee, VHF-
dc.contributor.authorLam, KO-
dc.contributor.authorKwan, CK-
dc.contributor.authorLi, WS-
dc.contributor.authorYau, S-
dc.contributor.authorBei, JX-
dc.contributor.authorLung, ML-
dc.date.accessioned2021-01-25T11:15:21Z-
dc.date.available2021-01-25T11:15:21Z-
dc.date.issued2020-
dc.identifier.citationCommunications Biology, 2020, v. 3, p. article no. 759-
dc.identifier.issn2399-3642-
dc.identifier.urihttp://hdl.handle.net/10722/295469-
dc.description.abstractDespite pronounced associations of major histocompatibility complex (MHC) regions with nasopharyngeal carcinoma (NPC), causal variants underlying NPC pathogenesis remain elusive. Our large-scale comprehensive MHC region deep sequencing study of 5689 Hong Kong Chinese identifies eight independent NPC-associated signals and provides mechanistic insight for disrupted transcription factor binding, altering target gene transcription. Two novel protective variants, rs2517664 (Trs2517664 = 4.6%, P = 6.38 × 10−21) and rs117495548 (Grs117495548 = 3.0%, P = 4.53 × 10−13), map near TRIM31 and TRIM39/TRIM39-RPP21; multiple independent protective signals map near HLA-B including a previously unreported variant, rs2523589 (P = 1.77 × 10−36). The rare HLA-B*07:05 allele (OR < 0.015, P = 5.83 × 10−21) is absent in NPC, but present in controls. The most prevalent haplotype lacks seven independent protective alleles (OR = 1.56) and the one with additional Asian-specific susceptibility rs9391681 allele (OR = 2.66) significantly increased NPC risk. Importantly, this study provides new evidence implicating two non-human leukocyte antigen (HLA) genes, E3 ubiquitin ligases, TRIM31 and TRIM39, impacting innate immune responses, with NPC risk reduction, independent of classical HLA class I/II alleles.-
dc.languageeng-
dc.publisherNature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/commsbio-
dc.relation.ispartofCommunications Biology-
dc.rightsCommunications Biology. Copyright © Nature Research: Fully open access journals.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleNasopharyngeal carcinoma MHC region deep sequencing identifies HLA and novel non-HLA TRIM31 and TRIM39 loci-
dc.typeArticle-
dc.identifier.emailKo, JMY: joko@hku.hk-
dc.identifier.emailYu, VZ: zvyu@hku.hk-
dc.identifier.emailNg, HY: hyng0812@hku.hk-
dc.identifier.emailChan, CKC: biocandy@hku.hk-
dc.identifier.emailNgan, RKC: rkcngan@hku.hk-
dc.identifier.emailKwong, DLW: dlwkwong@hku.hk-
dc.identifier.emailLee, AWM: awmlee@hkucc.hku.hk-
dc.identifier.emailNg, WT: ngwt1@hkucc.hku.hk-
dc.identifier.emailLee, VHF: vhflee@hku.hk-
dc.identifier.emailLam, KO: lamkaon@hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.authorityKo, JMY=rp02011-
dc.identifier.authorityYu, VZ=rp02756-
dc.identifier.authorityNgan, RKC=rp02371-
dc.identifier.authorityKwong, DLW=rp00414-
dc.identifier.authorityLee, AWM=rp02056-
dc.identifier.authorityNg, WT=rp02671-
dc.identifier.authorityLee, VHF=rp00264-
dc.identifier.authorityLam, KO=rp01501-
dc.identifier.authorityLung, ML=rp00300-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s42003-020-01487-y-
dc.identifier.pmid33311639-
dc.identifier.pmcidPMC7733486-
dc.identifier.scopuseid_2-s2.0-85097506665-
dc.identifier.hkuros320981-
dc.identifier.volume3-
dc.identifier.spagearticle no. 759-
dc.identifier.epagearticle no. 759-
dc.identifier.isiWOS:000599759700001-
dc.publisher.placeUnited Kingdom-

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