Association between ten-eleven methylcytosine dioxygenase 2 genetic variation and viral load in people with HIV. (1st March 2023)

• Record Type: Journal Article
• Authors: 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.
• Other Names: collaborator.
• Is Part Of: AIDS. Volume 37:Number 3(2023)
• Page Start: 379
• Page End: 387
• Publication Date: 2023-03-01
• Subjects: HIV -- ten-eleven methylcytosine dioxygenase 2 -- HIV viral load -- genetics -- transcriptional regulation; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000003427
• Languages: English
• ISSNs: 0269-9370

Abstract

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.