Crosstalk between Host Genome and Metabolome among People with HIV in South Africa

Abstract

Genome-wide association studies (GWAS) of circulating metabolites have revealed the role of genetic regulation on the human metabolome. Most previous investigations focused on European ancestry, and few studies have been conducted among populations of African descent living in Africa, where the infectious disease burden is high (e.g., human immunodeficiency virus (HIV)). It is important to understand the genetic associations of the metabolome in diverse at-risk populations including people with HIV (PWH) living in Africa. After a thorough literature review, the reported significant gene–metabolite associations were tested among 490 PWH in South Africa. Linear regression was used to test associations between the candidate metabolites and genetic variants. GWAS of 154 plasma metabolites were performed to identify novel genetic associations. Among the 29 gene–metabolite associations identified in the literature, we replicated 10 in South Africans with HIV. The UGT1A cluster was associated with plasma levels of biliverdin and bilirubin; SLC16A9 and CPS1 were associated with carnitine and creatine, respectively. We also identified 22 genetic associations with metabolites using a genome-wide significance threshold (p-value < 5 × 10−8). In a GWAS of plasma metabolites in South African PWH, we replicated reported genetic associations across ancestries, and identified novel genetic associations using a metabolomics approach.

Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results

“… 34 In all three cases, the frequency of the top associated SNP is larger in individuals of African descent than in Europeans according to the gnomAD Genomes database, but these hits were not found in the four largest mGWAS done in individuals of African ancestry to date. 35 , 36 , 37 , 38 We recognize that while interesting, these novel associations will need replication in an independent cohort.…”

Deproteinized Leaf Juice (DPJ): A Sustainable Resource for Nutrition, Medicine, and Agriculture

“…In the realm of agriculture, DPJ can be harnessed as a natural plant growth enhancer and pest repellent, reducing the reliance on chemical interventions (Silber et al,1970). In the pharmaceutical and nutraceutical industries, specific bioactive compounds identified in DPJ could be isolated and formulated for targeted therapeutic purposes (Liu et al, 2022).…”

“…It's worth noting that the selection of these plants for DPJ extraction aligns with centuries-old ethno pharmacological knowledge (Mungikar, 1974). Traditional uses of these plants by indigenous communities offer valuable insights into their bioactive potential (Liu et al, 2022). This synergy between traditional wisdom and modern science underscores the importance of preserving and integrating indigenous knowledge into contemporary research (Silber et al, 1970).…”

“…Variations in plant species, growing conditions, and extraction methods can lead to variations in DPJ composition (Ikram et al, 2023). Ensuring standardization and quality control is essential for consistency and reproducibility (Liu et al, 2022). Additionally, further research is needed to elucidate the precise mechanisms of action of DPJ's bioactive compounds and their potential interactions in complex biological systems (Jadhav et al, 1998).…”

“…Among these, Deproteinized Leaf Juice (DPJ) has taken center stage due to its versatility and utility in various applications, from dietary supplements to agriculture). In this review we endeavor to shed light on the diverse composition and potential benefits of DPJ from these plant sources (Liu et al, 2022).…”