Genetic variation near CXCL12 is associated with susceptibility to HIV-related non-Hodgkin lymphoma
| Autor: | Huldrych F. Günthard, Charles S. Rabkin, Federico Santoni, Manuel Battegay, Shehnaz K. Hussain, Patrick Schmid, Sophia S. Wang, Tiphaine Oudot-Mellakh, Andri Rauch, Cécile Goujard, Jonathan Niay, Enos Bernasconi, Christian W. Thorball, Caroline Besson, Matthias Hoffmann, Paul J. McLaren, Christian Hammer, Dominique Costagliola, Ioannis Theodorou, Laurence Meyer, Jacques Fellay, Matthias Cavassini |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
education.field_of_study T cell Population Genome-wide association study Biology medicine.disease 3. Good health Lymphoma 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure hemic and lymphatic diseases 030220 oncology & carcinogenesis Genetic variation Immunology BATF medicine education Viral load 030304 developmental biology Genetic association |
| DOI: | 10.1101/19011999 |
| Popis: | Human immunodeficiency virus (HIV) infection is associated with a substantially increased risk of non-Hodgkin lymphoma (NHL). High plasma viral load, low CD4+ T cell counts and absence of antiretroviral treatment (ART) are known predictive factors for NHL. Even in the era of suppressive ART, HIV-infected individuals remain at increased risk of developing NHL compared to the general population. To search for human genetic determinants of HIV-associated NHL, we performed case-control genome-wide association studies (GWAS) in three cohorts of HIV+ patients of European ancestry and meta-analyzed the results. In total, 278 cases and 1924 matched controls were included. We observed a significant association with NHL susceptibility in the C-X-C motif chemokine ligand 12 (CXCL12) region on chromosome 10. A fine mapping analysis identified rs7919208 as the most likely causal variant (P = 4.77e-11). The G>A polymorphism creates a new transcription factor binding site for BATF and JUND. Analyses of topologically associating domains and promoter capture Hi-C data revealed significant interactions between the rs7919208 region and the promoter of CXCL12, also known as stromal-derived factor 1 (SDF-1). These results suggest a modulatory role of CXCL12 regulation in the increased susceptibility to NHL observed in the HIV-infected population. |
| Databáze: | OpenAIRE |
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