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, S. Subathra, N. Punithavati, B. S. Tan, Y. S. Ee, L. M. Ong, R. A. HamidM. Goh, J. C.T. Quah, J. Lim, B. D. Dipak, R. Deepak, F. N. Lau, P. V. Kam, S. Shri Devi, C. A. Ong, C. L. Lum, N. A. Ahmad, S. Halimuddin, M. Somasundran, A. Kam, M. Wodjin, S. K. Subramaniam, T. S. Tiong, T. Y. Tan, U. H. Sim, T. W. Tharumalingam, D. Norlida, M. Zulkarnaen, W. H. Lai, A. Z. Bustam, S. Marniza, P. Shahfinaz, O. Hashim, S. Shamshinder, N. Prepageran, L. M. Looi, O. Rahmat, J. Amin, J. Maznan, S. Hassan, B. Biswal, A. Munirah, A. Subasri, L. P. Tan, N. M. Kumaran, M. S. Nurul Ashikin, M. S. Nursyazwani, B. Norhasimah, R. Sasela Devi, C. Y. Koh, Ching Ching Ng

研究成果: Article

24 引用 (Scopus)

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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.

元の言語English
ページ(範囲)678-687
ページ数10
ジャーナルInternational Journal of Cancer
136
発行部数3
DOI
出版物ステータスPublished - 15-02-2015

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Chin, Y. M., Mushiroda, T., Takahashi, A., Kubo, M., Krishnan, G., Yap, L. F., Teo, S. H., Lim, P. V. H., Yap, Y. Y., Pua, K. C., Kamatani, N., Nakamura, Y., Sam, C. K., Khoo, A. S. B., Subathra, S., Punithavati, N., Tan, B. S., Ee, Y. S., Ong, L. M., ... Ng, C. C. (2015). HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese. International Journal of Cancer, 136(3), 678-687. https://doi.org/10.1002/ijc.29035