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. 2023 Mar 1;37(3):379-387.
doi: 10.1097/QAD.0000000000003427. Epub 2022 Dec 7.

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

Daniel D Murray  1 , Birgit Grund  2 , Cameron R MacPherson  1 , Christina Ekenberg  1 , Adrian G Zucco  1 , Joanne Reekie  1 , Lourdes Dominguez-Dominguez  1 , Preston Leung  1 , Dahlene Fusco  3 , Julien Gras  4 , Jan Gerstoft  5 , Marie Helleberg  1   5 , Álvaro H Borges  1   6 , Mark N Polizzotto  7 , Jens D Lundgren  1 ; INSIGHT START, SMART, ESPRIT, STALWART study groups, and the FIRST study group
Affiliations

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

Daniel D Murray et al. AIDS. .

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.

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Conflict of interest statement

D.D.M., C.R.M, A.G.Z., J.R., M.H. and J.D.L. were supported by the Danish National Research Foundation (DNRF126). B.G. was supported by the National Institute of Health (UM1 AI120197). A.H.B. was supported by the Lundbeckfonden (grant number R219-2016-762). L.D.D. was supported by the EACS Medical Exchange Programme and the Spanish Society of Infectious Diseases and Clinical Microbiology. M.H. participated in advisory boards for AstraZeneca, Gilead, GSK, MSD, Roche and Sobi and received speakers honoraria from Gilead and GSK. M.P. received Funding from BMS, Celgene, Gilead, Janssen, ViiV Pharmaceuticals all outside submitted work (to institution). Provision of drug and other materials for studies from Astex/Otsuka, Celgene, CSL, Emergent Biosolutions, Janssen Grifols, Takeda, Verastem, ViiV Pharmaceuticals, all outside submitted work (to institution). Advisory board/speakers panel for Celgene, Gilead, outside submitted work. For the remaining authors, no conflicts relating to the submitted work were declared.

Figures

Fig. 1
Fig. 1
Associations between SNPs and markers of HIV pathogenesis.
Fig. 2
Fig. 2
Pairwise linkage disequilibrium (LD) analysis of SNPs significantly associated with VL in the START (a) and/or FIRST (b) cohorts.
See this image and copyright information in PMC

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