Association between ten-eleven methylcytosine dioxygenase 2 genetic variation and viral load in people with HIV
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Association between ten-eleven methylcytosine dioxygenase 2 genetic variation and viral load in people with HIV. / Murray, Daniel D; Grund, Birgit; Macpherson, Cameron R.; Ekenberg, Christina; Zucco, Adrian G.; Reekie, Joanne; Dominguez-Dominguez, Lourdes; Leung, Preston; Fusco, Dahlene; Gras, Julien; Gerstoft, Jan; Helleberg, Marie; Borges, Álvaro H.; Polizzotto, Mark N.; Lundgren, Jens D.
In: AIDS, Vol. 37, No. 3, 2023, p. 379-387.Research output: Contribution to journal › Journal article › Research › peer-review
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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 -
ID: 358551531