TY - JOUR

T1 - Association between ten-eleven methylcytosine dioxygenase 2 genetic variation and viral load in people with HIV

AU - Murray, Daniel D

AU - Grund, Birgit

AU - Macpherson, Cameron R.

AU - Ekenberg, Christina

AU - Zucco, Adrian G.

AU - Reekie, Joanne

AU - Dominguez-Dominguez, Lourdes

AU - Leung, Preston

AU - Fusco, Dahlene

AU - Gras, Julien

AU - Gerstoft, Jan

AU - Helleberg, Marie

AU - Borges, Álvaro H.

AU - Polizzotto, Mark N.

AU - Lundgren, Jens D.

N1 - Funding Information: Funding: This study was funded by the Danish National Research Foundation (DNRF126). The clinical trials described in this study were supported by the National Institute of Health (UM1-AI06864, UM1-AI120197, 1U01-AI36780, U01-AI46957, U01-AI042170, U01-AI046362), National Institute of Allergy and Infectious Diseases, National Institutes of Health Clinical Center, National Cancer Institute, National Heart, Lung, and Blood Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), National Health and Medical Research Council (Australia), National Research Foundation (Denmark), Bundes ministerium für Bildung und Forschung (Germany), European AIDS Treatment Network, Medical Research Council (United Kingdom), National Institute for Health Research, National Health Service (United Kingdom), and University of Minnesota. Antiretroviral drugs were donated to the central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, and Merck. Funding Information: 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. Publisher Copyright: © Copyright 2023 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - genetics

KW - HIV

KW - HIV viral load

KW - ten-eleven methylcytosine dioxygenase 2

KW - transcriptional regulation

U2 - 10.1097/QAD.0000000000003427

DO - 10.1097/QAD.0000000000003427

M3 - Journal article

C2 - 36473831

AN - SCOPUS:85147047839

VL - 37

SP - 379

EP - 387

JO - AIDS

JF - AIDS

SN - 1350-2840

IS - 3

ER -