ArticleAIDS (London, England)2016
Host genetic predictors of the kynurenine pathway of tryptophan catabolism among treated HIV-infected Ugandans.
Article in AIDS (London, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Host Genetic Regulation of NLRP3 Inflammasome Cytokines Reveals Immune and Vascular Pathways in HIV.medRxiv : the preprint server for health sciences · 2026Article
- A Rare Case of Polymicrogyria in an Elderly Individual With Unique Polygenic Underlining.Cureus · 2024Article
- Inflammation and microbial translocation measured prior to combination antiretroviral therapy (cART) and long-term probability of clinical progression in people living with HIV.BMC infectious diseases · 2021Article
- The Current State of HIV and Aging: Findings Presented at the 10th International Workshop on HIV and Aging.AIDS research and human retroviruses · 2020Article
- Article
- Changes in Deoxyribonucleic Acid Methylation Contribute to the Pathophysiology of Multiple Sclerosis.Frontiers in genetics · 2019Review
- Aging, Health, and Quality of Life for Older People Living With HIV in Sub-Saharan Africa: A Review and Proposed Conceptual Framework.Journal of aging and health · 2019Article
- Kynurenine Pathway Metabolites as Biomarkers for Amyotrophic Lateral Sclerosis.Frontiers in neuroscience · 2019Review
- CYP2B6 Genetic Polymorphisms, Depression, and Viral Suppression in Adults Living with HIV Initiating Efavirenz-Containing Antiretroviral Therapy Regimens in Uganda: Pooled Analysis of Two Prospective Studies.AIDS research and human retroviruses · 2018Article
- Immunologic Pathways That Predict Mortality in HIV-Infected Ugandans Initiating Antiretroviral Therapy.The Journal of infectious diseases · 2017Article
- HIV/Human herpesvirus co-infections: Impact on tryptophan-kynurenine pathway and immune reconstitution.PloS one · 2017Article
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
Abstract
objectivePlasma kynurenine/tryptophan ratio, a biomarker of indoleamine 2,3-dioxygenase-1 (IDO) activity, is a strong independent predictor of mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART) and may play a key role in HIV pathogenesis. We performed a genome-wide study to identify potential host genetic determinants of kynurenine/tryptophan ratio in HIV-infected ART-suppressed Ugandans. DESIGN/
methodsWe performed genome-wide and exome array genotyping and measured plasma kynurenine/tryptophan ratio during the initial 6-12 months of suppressive ART in Ugandans. We evaluated more than 16 million single nucleotide polymorphisms in association with log10 kynurenine/tryptophan ratio using linear mixed models adjusted for cohort, sex, pregnancy, and ancestry.
resultsAmong 597 Ugandans, 62% were woman, median age was 35, median baseline CD4 cell count was 135 cells/μl, and median baseline HIV-1 RNA was 5.1 log10 copies/ml. Several polymorphisms in candidate genes TNF, IFNGR1, and TLR4 were associated with log10 kynurenine/tryptophan ratio (P < 5.0 × 10). An intergenic polymorphism between CSPG5 and ELP6 was genome-wide significant, whereas several others exhibited suggestive associations (P < 5.0 × 10), including genes encoding protein tyrosine phosphatases (PTPRM and PTPRN2) and the vitamin D metabolism gene, CYP24A1. Several of these single nucleotide polymorphisms were associated with markers of inflammation, coagulation, and monocyte activation, but did not replicate in a small US cohort (N = 262; 33% African-American).
conclusionOur findings highlight a potentially important role of IFN-γ, TNF-α, and Toll-like receptor signaling in determining IDO activity and subsequent mortality risk in HIV-infected ART-suppressed Ugandans. These results also identify potential novel pathways involved in IDO immunoregulation. Further studies are needed to confirm these findings in treated HIV-infected populations.
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