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

doi:10.1097/QAD.0000000000003427

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

Department of Infectious Diseases

2 Citations (Scopus)

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 language	English
Journal	AIDS
Volume	37
Issue number	3
Pages (from-to)	379-387
Number of pages	9
ISSN	0269-9370
DOIs	https://doi.org/10.1097/QAD.0000000000003427
Publication status	Published - 1 Mar 2023

Keywords

HIV
HIV viral load
genetics
ten-eleven methylcytosine dioxygenase 2
transcriptional regulation

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10.1097/QAD.0000000000003427

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Murray, D. D., Grund, B., MacPherson, C., Ekenberg, C., Zucco, A., Reekie, J., Dominguez-Dominguez, L., Leung, P., Fusco, D., Gras, J., Gerstoft, J., Helleberg, M., Borges, Á. H., Polizzotto, M., Lundgren, J. D., & INSIGHT START, SMART, ESPRIT, STALWART study groups, the FIRST study group (2023). Association between ten-eleven methylcytosine dioxygenase 2 genetic variation and viral load in people with HIV. AIDS, 37(3), 379-387. https://doi.org/10.1097/QAD.0000000000003427

Murray, DD, Grund, B, MacPherson, C, Ekenberg, C , Zucco, A , Reekie, J, Dominguez-Dominguez, L, Leung, P, Fusco, D, Gras, J, Gerstoft, J , Helleberg, M , Borges, ÁH, Polizzotto, M, Lundgren, JD & INSIGHT START, SMART, ESPRIT, STALWART study groups, the FIRST study group 2023, 'Association between ten-eleven methylcytosine dioxygenase 2 genetic variation and viral load in people with HIV', AIDS, vol. 37, no. 3, pp. 379-387. https://doi.org/10.1097/QAD.0000000000003427

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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-na{\"i}ve 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.",

keywords = "HIV, HIV viral load, genetics, ten-eleven methylcytosine dioxygenase 2, transcriptional regulation",

author = "Murray, \{Daniel D\} and Birgit Grund and Cameron MacPherson and Christina Ekenberg and Adrian Zucco and Joanne Reekie and Lourdes Dominguez-Dominguez and Preston Leung and Dahlene Fusco and Julien Gras and Jan Gerstoft and Marie Helleberg and Borges, \{{\'A}lvaro H\} and Mark Polizzotto and Lundgren, \{Jens D\} and \{INSIGHT START, SMART, ESPRIT, STALWART study groups, the FIRST study group\}",

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doi = "10.1097/QAD.0000000000003427",

language = "English",

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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

AU - Ekenberg, Christina

AU - Zucco, Adrian

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

AU - Lundgren, Jens D

AU - INSIGHT START, SMART, ESPRIT, STALWART study groups, the FIRST study group

PY - 2023/3/1

Y1 - 2023/3/1

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 - HIV

KW - HIV viral load

KW - genetics

KW - ten-eleven methylcytosine dioxygenase 2

KW - transcriptional regulation

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U2 - 10.1097/QAD.0000000000003427

DO - 10.1097/QAD.0000000000003427

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SN - 0269-9370

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SP - 379

EP - 387

JO - AIDS

JF - AIDS

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ER -

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

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Keywords

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