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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley-Liss Inc.
2015
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| Subjects: | |
| Online Access: | http://ir.unimas.my/id/eprint/14913/ http://ir.unimas.my/id/eprint/14913/7/ming.pdf |
| _version_ | 1848837752936726528 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yoon-Ming, Chin |
| building | UNIMAS Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-15T06:44:40Z |
| format | Article |
| id | unimas-14913 |
| institution | Universiti Malaysia Sarawak |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T06:44:40Z |
| publishDate | 2015 |
| publisher | Wiley-Liss Inc. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | unimas-149132021-05-21T12:02:03Z http://ir.unimas.my/id/eprint/14913/ HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese 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 RB Pathology 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. Wiley-Liss Inc. 2015 Article PeerReviewed text en http://ir.unimas.my/id/eprint/14913/7/ming.pdf Yoon-Ming, Chin and Taisei, Mushiroda and Atsushi, Takahashi and Michiaki, Kubo and Gopala, Krishnan and Lee-Fah, Yap and Soo-Hwang, Teo and Paul Vey-Hong, Lim and Yoke-Yeow, Yap and Kin-Choo, Pua and Naoyuki, Kamatani and Yusuke, Nakamura and Choon-Kook, Sam and Alan Soo-Beng, Khoo and Ching-Ching, Ng (2015) HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese. International Journal of Cancer, 136 (3). pp. 678-687. ISSN 207136 http://www.scopus.com/inward/record.url?eid=2-s2.0-84911005348&partnerID=40&md5=d19bfa01334f9a7c0a0ab85ca4aeb252 |
| spellingShingle | RB Pathology 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 HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese |
| title | HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese |
| title_full | HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese |
| title_fullStr | HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese |
| title_full_unstemmed | HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese |
| title_short | HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese |
| title_sort | hla-a snps and amino acid variants are associated with nasopharyngeal carcinoma in malaysian chinese |
| topic | RB Pathology |
| url | http://ir.unimas.my/id/eprint/14913/ http://ir.unimas.my/id/eprint/14913/ http://ir.unimas.my/id/eprint/14913/7/ming.pdf |