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Determining the role of differential expression of candidate icroRNAs in cardiometabolic diseases among South African adults living with HIV

Background: MicroRNAs (miRNAs) are potential prognostic/diagnostic markers that have been investigated for screening of cardiometabolic disease (CMD) risk in general populations. However, little is known about their value in people living with human immunodeficiency virus (PLWH), who have an increas...

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Main Author: Govender, Leegan
Other Authors: Dandara, Collet
Format: Thesis
Language:Eng
Published: Department of Pathology 2025
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Medicine
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access_status_str Open Access
author Govender, Leegan
author2 Dandara, Collet
author_browse Dandara, Collet
Govender, Leegan
author_facet Dandara, Collet
Govender, Leegan
author_sort Govender, Leegan
collection Thesis
description Background: MicroRNAs (miRNAs) are potential prognostic/diagnostic markers that have been investigated for screening of cardiometabolic disease (CMD) risk in general populations. However, little is known about their value in people living with human immunodeficiency virus (PLWH), who have an increased susceptibility to CMDs. PLWH have an increased susceptibility to CMDs because of chronic inflammation caused by a persistent immune response, metabolic complications from antiretroviral therapies, and traditional risk factors. In this study the association of differential expression of candidate miRNAs, miR-126-3p, -223-3p, and -320a with CMDs was investigated among PLWH. Methods: Using a cross-sectional study design ≥18-year-old PLWH were recruited from 17 random HIV clinics in the Western Cape, South Africa between 2014-2015. Standard international definitions were used to diagnose CMDs. Whole blood miRNAs were isolated, and expression quantified by reverse transcription quantitative polymerase chain reaction. MiRNA expression was compared between participants with a CMD and without for each investigated outcome, using Wilcoxon rank sum/Kruskal Wallis tests. Robust correlations, robust linear regressions and logistic regressions assessed miRNAs relationships with cardiometabolic risk profiles. A p-value <0.05 was considered statistically significant. Results: Among 675 participants (81% women), prevalence of CMDs/traits was: elevated highsensitivity C-reactive protein (67.4%), raised waist circumference (WC) (63.3%), obesity (34.1%), insulin resistance (IR) (9.9%), and diabetes mellitus (8.6%). Target miRNAs were not significantly differentially expressed based on individual CMD statuses. However, target miRNAs were significantly correlated with glucose homeostasis variables [fasting glucose (r≤0.129, p≤0.046); fasting insulin (r≤0.115, p≤0.015); 2-hour insulin (r≤0.097, p≤0.029); and homeostatic model assessment of insulin resistance (HOMA-IR) (r≤0.144, p≤0.002)], and miR126-3p and -223-3p were significantly correlated with alanine transaminase (r≤0.128, p≤0.022). In linear regression models after adjusted for age and gender, miR-126-3p had a borderline association with HOMA-IR (β≤0.018, p≤0.081), while miR-223-3p was borderline associated with glucose when adjusted for age, gender, and WC (β=0.001, p=0.066). There were no significant associations in logistic regression models. Conclusion: The miRNAs tested in this study appear not to be important markers for CMDs in PLWH. A genome-wide approach is recommended to uncover other miRNAs with potential as biomarkers of CMDs in PLWH.
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language Eng
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license_str Not specified — see source repository
provenance_str_mv Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository
publishDate 2025
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spelling oai:open.uct.ac.za:11427/40955 Determining the role of differential expression of candidate icroRNAs in cardiometabolic diseases among South African adults living with HIV Govender, Leegan Dandara, Collet kengne Andre Medicine Background: MicroRNAs (miRNAs) are potential prognostic/diagnostic markers that have been investigated for screening of cardiometabolic disease (CMD) risk in general populations. However, little is known about their value in people living with human immunodeficiency virus (PLWH), who have an increased susceptibility to CMDs. PLWH have an increased susceptibility to CMDs because of chronic inflammation caused by a persistent immune response, metabolic complications from antiretroviral therapies, and traditional risk factors. In this study the association of differential expression of candidate miRNAs, miR-126-3p, -223-3p, and -320a with CMDs was investigated among PLWH. Methods: Using a cross-sectional study design ≥18-year-old PLWH were recruited from 17 random HIV clinics in the Western Cape, South Africa between 2014-2015. Standard international definitions were used to diagnose CMDs. Whole blood miRNAs were isolated, and expression quantified by reverse transcription quantitative polymerase chain reaction. MiRNA expression was compared between participants with a CMD and without for each investigated outcome, using Wilcoxon rank sum/Kruskal Wallis tests. Robust correlations, robust linear regressions and logistic regressions assessed miRNAs relationships with cardiometabolic risk profiles. A p-value <0.05 was considered statistically significant. Results: Among 675 participants (81% women), prevalence of CMDs/traits was: elevated highsensitivity C-reactive protein (67.4%), raised waist circumference (WC) (63.3%), obesity (34.1%), insulin resistance (IR) (9.9%), and diabetes mellitus (8.6%). Target miRNAs were not significantly differentially expressed based on individual CMD statuses. However, target miRNAs were significantly correlated with glucose homeostasis variables [fasting glucose (r≤0.129, p≤0.046); fasting insulin (r≤0.115, p≤0.015); 2-hour insulin (r≤0.097, p≤0.029); and homeostatic model assessment of insulin resistance (HOMA-IR) (r≤0.144, p≤0.002)], and miR126-3p and -223-3p were significantly correlated with alanine transaminase (r≤0.128, p≤0.022). In linear regression models after adjusted for age and gender, miR-126-3p had a borderline association with HOMA-IR (β≤0.018, p≤0.081), while miR-223-3p was borderline associated with glucose when adjusted for age, gender, and WC (β=0.001, p=0.066). There were no significant associations in logistic regression models. Conclusion: The miRNAs tested in this study appear not to be important markers for CMDs in PLWH. A genome-wide approach is recommended to uncover other miRNAs with potential as biomarkers of CMDs in PLWH. 2025-02-13T13:15:43Z 2025-02-13T13:15:43Z 2024 2025-02-13T12:57:12Z Thesis / Dissertation Masters MSc http://hdl.handle.net/11427/40955 Eng application/pdf Department of Pathology Faculty of Health Sciences University of Cape Town
spellingShingle Medicine
Govender, Leegan
Determining the role of differential expression of candidate icroRNAs in cardiometabolic diseases among South African adults living with HIV
thesis_degree_str Master's
title Determining the role of differential expression of candidate icroRNAs in cardiometabolic diseases among South African adults living with HIV
title_full Determining the role of differential expression of candidate icroRNAs in cardiometabolic diseases among South African adults living with HIV
title_fullStr Determining the role of differential expression of candidate icroRNAs in cardiometabolic diseases among South African adults living with HIV
title_full_unstemmed Determining the role of differential expression of candidate icroRNAs in cardiometabolic diseases among South African adults living with HIV
title_short Determining the role of differential expression of candidate icroRNAs in cardiometabolic diseases among South African adults living with HIV
title_sort determining the role of differential expression of candidate icrornas in cardiometabolic diseases among south african adults living with hiv
topic Medicine
url http://hdl.handle.net/11427/40955
work_keys_str_mv AT govenderleegan determiningtheroleofdifferentialexpressionofcandidateicrornasincardiometabolicdiseasesamongsouthafricanadultslivingwithhiv

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