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Title: | Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma |
Authors: | Liu, Zhiwei Luo, Yang Kirimunda, Samuel Verboom, Murielle Onabajo, lusegun O. Gouveia, Mateus H. Ogwang, Martin D. Kerchan, Patrick Reynolds, Steven J. Tenge, Constance N Were, Pamela A. Kuremu, Robert T. Wekesa, Walter N. Masalu, Nestory Kawira, Esther Kinyera, Tobias Otim, Isaac Legason, Ismail D Nabalende, Hadijah Dhudha, Herry Ayers, Leona W. Bhatia, Kishor Goedert, James J. Cole, Nathan Luo, Wen Liu, Jia Manning, Michelle Hicks, Belynda Prokunina-Olsson, Ludmila Chagaluka, George Johnston, W. Thomas J Mutalima, Nora Borgstein, Eric Liomba, George N. Kamiza, Steve Mkandawire, Nyengo Mitambo, Collins Molyneux, Elizabeth M Newton, , Robert Hsing, Ann W. . Mensah, James E Adjei, Anthony A. Hutchinson, Amy Carrington, Mary Yeage, Meredith Blasczyk, Rainer . Chanock, Stephen J Raychaudhuri, Soumya Mbulaiteye, Sam M. |
Keywords: | Burkitt lymphoma Childhood cancers Chronic infection |
Issue Date: | 5-Jan-2024 |
Publisher: | Springer |
Abstract: | Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which reg- ulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10−6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10−8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10−6 ). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control. |
URI: | https://doi.org/10.1038/s42003-023-05701-5 http://ir.mu.ac.ke:8080/jspui/handle/123456789/9103 |
Appears in Collections: | School of Medicine |
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