201. Genetic Variations in EIF2AK3 are Associated with Neurocognitive Impairment in People Living with HIV.
- Author
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Akay-Espinoza, Cagla, Newton, Sarah, Dombroski, Beth, Kallianpur, Asha, Bharti, Ajay, Franklin, Donald, Schellenberg, Gerard, Heaton, Robert, Grant, Igor, Ellis, Ronald, Letendre, Scott, and Jordan-Sciutto, Kelly
- Subjects
EIF2AK3 ,HIV ,Haplotype ,Integrated stress response ,Neurocognitive impairment ,Single nucleotide variant ,Humans ,Female ,Male ,eIF-2 Kinase ,Adult ,HIV Infections ,Middle Aged ,Polymorphism ,Single Nucleotide ,Retrospective Studies ,Cohort Studies ,Cognitive Dysfunction - Abstract
Based on emerging evidence on the role for specific single-nucleotide variants (SNVs) in EIF2AK3 encoding the integrated stress response kinase PERK, in neurodegeneration, we assessed the association of EIF2AK3 SNVs with neurocognitive performance in people with HIV (PWH) using a candidate gene approach. This retrospective study included the CHARTER cohort participants, excluding those with severe neuropsychiatric comorbidities. Genome-wide data previously obtained for 1047 participants and targeted sequencing of 992 participants with available genomic DNA were utilized to interrogate the association of three noncoding and three coding EIF2AK3 SNVs with the continuous global deficit score (GDS) and global neurocognitive impairment (NCI; GDS ≥ 0.5) using univariable and multivariable methods, with demographic, disease-associated, and treatment characteristics as covariates. The cohort characteristics were as follows: median age, 43.1 years; females, 22.8%; European ancestry, 41%; median CD4 + T cell counts, 175/µL (nadir) and 428/µL (current). At first assessment, 70.5% used ART and 68.3% of these had plasma HIV RNA levels ≤ 200 copies/mL. All three noncoding EIF2AK3 SNVs were associated with GDS and NCI (all p 13 were independently associated with GDS and NCI (p
- Published
- 2024