The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove

Minzhong Tang, James A. Lautenberger, Xiaojiang Gao, Efe Sezgin, Sher L. Hendrickson, Jennifer L. Troyer, Victor A. David, Li Guan, Carl E. Mcintosh, Xiuchan Guo, Yuming Zheng, Jian Liao, Hong Deng, Michael Malasky, Bailey Kessing, Cheryl A. Winkler, Mary Carrington, Guy dé The, Yi Zeng, Stephen J. O'Brien

Research output: Contribution to journalArticle

Abstract

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 (PHLA-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.

Original languageEnglish (US)
Article numbere1003103
JournalPLoS Genetics
Volume8
Issue number11
DOIs
StatePublished - Nov 2012
Externally publishedYes

Fingerprint

Histocompatibility Antigens Class I
HLA-B Antigens
HLA Antigens
antigen
HLA-A Antigens
carcinoma
China
amino acid
antigens
Amino Acids
amino acids
peptide
HLA-C Antigens
MHC Class I Genes
allele
gene
Alleles
peptides
alleles
Peptides

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Tang, M., Lautenberger, J. A., Gao, X., Sezgin, E., Hendrickson, S. L., Troyer, J. L., ... O'Brien, S. J. (2012). The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove. PLoS Genetics, 8(11), [e1003103]. https://doi.org/10.1371/journal.pgen.1003103

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.

In: PLoS Genetics, Vol. 8, No. 11, e1003103, 11.2012.

Research output: Contribution to journalArticle

Tang, M, Lautenberger, JA, Gao, X, Sezgin, E, Hendrickson, SL, Troyer, JL, David, VA, Guan, L, Mcintosh, CE, Guo, X, Zheng, Y, Liao, J, Deng, H, Malasky, M, Kessing, B, Winkler, CA, Carrington, M, dé The, G, Zeng, Y & O'Brien, SJ 2012, 'The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove', PLoS Genetics, vol. 8, no. 11, e1003103. https://doi.org/10.1371/journal.pgen.1003103
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. In: PLoS Genetics. 2012 ; Vol. 8, No. 11.
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AU - Malasky, Michael

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