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

Department of Infectious Diseases

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

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

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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.",

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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.

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KW - Dioxygenases/genetics

KW - HIV Infections/drug therapy

KW - Humans

KW - Polymorphism, Single Nucleotide

KW - Viral Load

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DO - 10.1097/QAD.0000000000003427

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JO - AIDS

JF - AIDS

SN - 0269-9370

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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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