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The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing i...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510037/ https://www.ncbi.nlm.nih.gov/pubmed/23209447 http://dx.doi.org/10.1371/journal.pgen.1003103 |
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author | Tang, Minzhong Lautenberger, James A. Gao, Xiaojiang Sezgin, Efe Hendrickson, Sher L. Troyer, Jennifer L. David, Victor A. Guan, Li Mcintosh, Carl E. Guo, Xiuchan Zheng, Yuming Liao, Jian Deng, Hong Malasky, Michael Kessing, Bailey Winkler, Cheryl A. Carrington, Mary dé The, Guy Zeng, Yi O'Brien, Stephen J. |
author_facet | Tang, Minzhong Lautenberger, James A. Gao, Xiaojiang Sezgin, Efe Hendrickson, Sher L. Troyer, Jennifer L. David, Victor A. Guan, Li Mcintosh, Carl E. Guo, Xiuchan Zheng, Yuming Liao, Jian Deng, Hong Malasky, Michael Kessing, Bailey Winkler, Cheryl A. Carrington, Mary dé The, Guy Zeng, Yi O'Brien, Stephen J. |
author_sort | Tang, Minzhong |
collection | PubMed |
description | Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA –B, and HLA -C class I genes (P(HLA-A-aa-site-62) = 7.4×10(−29); P (HLA-B-aa-site-116) = 6.5×10(−19); P (HLA-C-aa-site-156) = 6.8×10(−8) respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China. |
format | Online Article Text |
id | pubmed-3510037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35100372012-12-03 The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove Tang, Minzhong Lautenberger, James A. Gao, Xiaojiang Sezgin, Efe Hendrickson, Sher L. Troyer, Jennifer L. David, Victor A. Guan, Li Mcintosh, Carl E. Guo, Xiuchan Zheng, Yuming Liao, Jian Deng, Hong Malasky, Michael Kessing, Bailey Winkler, Cheryl A. Carrington, Mary dé The, Guy Zeng, Yi O'Brien, Stephen J. PLoS Genet Research Article Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA –B, and HLA -C class I genes (P(HLA-A-aa-site-62) = 7.4×10(−29); P (HLA-B-aa-site-116) = 6.5×10(−19); P (HLA-C-aa-site-156) = 6.8×10(−8) respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China. Public Library of Science 2012-11-29 /pmc/articles/PMC3510037/ /pubmed/23209447 http://dx.doi.org/10.1371/journal.pgen.1003103 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Tang, Minzhong Lautenberger, James A. Gao, Xiaojiang Sezgin, Efe Hendrickson, Sher L. Troyer, Jennifer L. David, Victor A. Guan, Li Mcintosh, Carl E. Guo, Xiuchan Zheng, Yuming Liao, Jian Deng, Hong Malasky, Michael Kessing, Bailey Winkler, Cheryl A. Carrington, Mary dé The, Guy Zeng, Yi O'Brien, Stephen J. The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove |
title | The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove |
title_full | The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove |
title_fullStr | The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove |
title_full_unstemmed | The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove |
title_short | The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove |
title_sort | principal genetic determinants for nasopharyngeal carcinoma in china involve the hla class i antigen recognition groove |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510037/ https://www.ncbi.nlm.nih.gov/pubmed/23209447 http://dx.doi.org/10.1371/journal.pgen.1003103 |
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