Association between ten-eleven methylcytosine dioxygenase 2 genetic variation and viral load in people with HIV

Daniel D Murray*, Birgit Grund, Cameron MacPherson, Christina Ekenberg, Adrian Zucco, Joanne Reekie, Lourdes Dominguez-Dominguez, Preston Leung, Dahlene Fusco, Julien Gras, Jan Gerstoft, Marie Helleberg, Álvaro H Borges, Mark Polizzotto, Jens D Lundgren, INSIGHT START, SMART, ESPRIT, STALWART study groups, the FIRST study group

*Corresponding author for this work

Abstract

INTRODUCTION: Identifying genetic factors that influence HIV-pathogenesis is critical for understanding disease pathways. Previous studies have suggested a role for the human gene ten-eleven methylcytosine dioxygenase 2 (TET2) in modulating HIV-pathogenesis.

METHODS: We assessed whether genetic variation in TET2 was associated with markers of HIV-pathogenesis using both gene level and single nucleotide polymorphism (SNP) level association in 8512 HIV-positive persons across five clinical trial cohorts.

RESULTS: Variation at both the gene and SNP-level of TET2 was found to be associated with levels of HIV viral load (HIV-VL) consistently in the two cohorts that recruited antiretroviral-naïve participants. The SNPs occurred in two clusters of high linkage disequilibrium (LD), one associated with high HIV-VL and the other low HIV-VL, and were predominantly found in Black participants.

CONCLUSION: Genetic variation in TET2 was associated with HIV-VL in two large antiretroviral therapy (ART)-naive clinical trial cohorts. The role of TET2 in HIV-pathogenesis warrants further investigation.

Original languageEnglish
JournalAIDS
Volume37
Issue number3
Pages (from-to)379-387
Number of pages9
ISSN0269-9370
DOIs
Publication statusPublished - 1 Mar 2023

Keywords

  • CD4 Lymphocyte Count
  • Dioxygenases/genetics
  • HIV Infections/drug therapy
  • Humans
  • Polymorphism, Single Nucleotide
  • Viral Load

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