Genetic variation near CXCL12 is associated with susceptibility to HIV-related non-Hodgkin lymphoma

Haematologica. 2021 Aug 1;106(8):2233-2241. doi: 10.3324/haematol.2020.247023.

Abstract

Human immunodeficiency virus (HIV) infection is associated with an increased risk of non-Hodgkin lymphoma (NHL). Even in the era of suppressive antiretroviral treatment, HIV-infected individuals remain at higher risk of developing NHL compared to the general population. To identify potential genetic risk loci, we performed case-control genome-wide association studies and a meta-analysis across three cohorts of HIV+ patients of European ancestry, including a total of 278 cases and 1924 matched controls. 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), with the G>A polymorphism creating a new transcription factor binding site for BATF and JUND. These results suggest a modulatory role of CXCL12 regulation in the increased susceptibility to NHL observed in the HIV-infected population.

Publication types

  • Meta-Analysis

MeSH terms

  • Anti-Retroviral Agents / therapeutic use
  • Case-Control Studies
  • Chemokine CXCL12
  • Genome-Wide Association Study
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • HIV Infections* / genetics
  • Humans
  • Lymphoma, AIDS-Related* / drug therapy
  • Lymphoma, Non-Hodgkin* / drug therapy
  • Lymphoma, Non-Hodgkin* / genetics
  • Polymorphism, Genetic

Substances

  • Anti-Retroviral Agents
  • CXCL12 protein, human
  • Chemokine CXCL12