HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese

HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese

Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1) infection. We carried out a genome-wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysia...

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Bibliographic Details
Main Authors: Yoon-Ming, Chin, Taisei, Mushiroda, Atsushi, Takahashi, Michiaki, Kubo, Gopala, Krishnan, Lee-Fah, Yap, Soo-Hwang, Teo, Paul Vey-Hong, Lim, Yoke-Yeow, Yap, Kin-Choo, Pua, Naoyuki, Kamatani, Yusuke, Nakamura, Choon-Kook, Sam, Alan Soo-Beng, Khoo, Ching-Ching, Ng
Format: Article
Language:English
Published: Wiley-Liss Inc. 2015
Subjects:
RB Pathology
Online Access:http://ir.unimas.my/id/eprint/14913/
http://ir.unimas.my/id/eprint/14913/7/ming.pdf
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Summary:Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1) infection. We carried out a genome-wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA-A to NPC with the strongest signal detected in rs3869062 (p=1.73 3 10-9). HLA-A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (pHLA-A-aa-site-99=3.79 × 10-8, prs1136697=3.79 × 10-8) and T-cell receptor binding site (pHLA-A-aa-site-145=1.41 × 1024, prs1059520=1.41 × 10-4) of the HLA-A. We also detected strong association signals in the 50-UTR region with predicted active promoter states (prs41545520=7.91 × 10-8). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520-G correlated with reduced HLA-A expression. Multivariate logistic regression diminished the effects of HLA-A amino acid variants and SNPs, indicating a correlation with the effects of HLA-A∗11:01, and to a lesser extent HLA-A∗02:07. We report the strong genetic influence of HLA-A on NPC susceptibility in the Malaysian Chinese. © 2014 UICC.

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