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.
To cite this publication, please use the following BibTeX entry:
@article{murrayAssociationTenelevenMethylcytosine2023,
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.},
author = {Murray, Daniel D. and Grund, Birgit and MacPherson, Cameron R. and Ekenberg, Christina and Zucco, Adrian G. and Reekie, Joanne and Dominguez-Dominguez, Lourdes and Leung, Preston and Fusco, Dahlene and Gras, Julien and Gerstoft, Jan and Helleberg, Marie and Borges, Álvaro H. and Polizzotto, Mark N. and Lundgren, Jens D.},
doi = {10.1097/QAD.0000000000003427},
issn = {0269-9370},
journal = {AIDS},
langid = {american},
month = {March},
number = {3},
pages = {379},
title = {Association between Ten-Eleven Methylcytosine Dioxygenase 2 Genetic Variation and Viral Load in People with HIV},
urldate = {2023-03-11},
volume = {37},
year = {2023}
}