Dataset Information

Associations of gamma-glutamyl transferase with cardio-metabolic diseases in people living with HIV infection in South Africa.

ABSTRACT:

Background

Gamma-glutamyl transferase (GGT) has recently been reported as a biomarker for cardiovascular (CVD) risk in general populations. We investigated the associations of GGT with cardio-metabolic diseases and CVD risk in South Africans living with HIV.

Methods

In this cross-sectional study, HIV-infected adults were randomly recruited across 17 HIV clinics in the Western Cape Province. Homeostatic model assessment for insulin resistance (HOMA-IR), hypertension, diabetes, metabolic syndrome by Joint Interim Statement criteria (JIS-MS), a ?5% and ?10% predicted risk for a CVD event within 10 years by the Framingham risk score (10-years-CVD risk) were computed. Associations between GGT and cardio-metabolic trait were explored using linear and binomial logistic regressions adjusted for age, gender, lifestyle behaviours and HIV-related characteristics.

Results

Among 709 participants (561 women, mean age 38.6 years), log-GGT was positively associated with waist circumference (?=2.75; p<0.001), diastolic blood pressure (?=1.65; p=0.006), total cholesterol (?=0.21; p<0.001), low-density lipoprotein-cholesterol (?=0.16; p<0.001), high-density lipoprotein-cholesterol and log-triglycerides (both ?=0.12; p<0.001), fasting plasma glucose (?=0.19; p=0.031), 2-hour-post-glucose-load plasma glucose (?=0.26; p=0.007), HOMA-IR (?=0.13; p=0.001), log-high-sensitivity C-reactive-protein (?=0.3; p<0.001) in linear regression analyses; with hypertension [OR=1.41 (95%CI, 1.13-1.75); p=0.001], JIS-MS [OR=1.33 (1.05-1.68); p=0.016], ?5% 10-year-CVD risk [OR=1.55 (1.24-1.9400); p<0.001] and ?10% 10-year-CVD risk [OR=1.56 (1.08-2.23); p=0.016] but not with diabetes [OR=1.24 (0.88-1.71), p=0.205] in logistic regression analyses.

Conclusions

In this study, GGT levels were associated with cardio-metabolic variables independent of HIV specific attributes. If confirmed in longitudinal studies, GGT evaluation maybe included in CVD risk monitoring strategies in people living with HIV.

SUBMITTER: Nguyen KA

PROVIDER: S-EPMC7864415 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Associations of gamma-glutamyl transferase with cardio-metabolic diseases in people living with HIV infection in South Africa.

Nguyen Kim A KA Peer Nasheeta N Kengne Andre P AP

PloS one 20210205 2

<h4>Background</h4>Gamma-glutamyl transferase (GGT) has recently been reported as a biomarker for cardiovascular (CVD) risk in general populations. We investigated the associations of GGT with cardio-metabolic diseases and CVD risk in South Africans living with HIV.<h4>Methods</h4>In this cross-sectional study, HIV-infected adults were randomly recruited across 17 HIV clinics in the Western Cape Province. Homeostatic model assessment for insulin resistance (HOMA-IR), hypertension, diabetes, meta ...[more]

PMID: 33544719

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Project description:AimsTo describe the distribution and examine the associations of diabetes, hypertension and hypercholesterolaemia across and within population groups, gender and body mass index (BMI) categories.MethodsThis national cross-sectional study was conducted in 2013 among ≥18-year-old black African, coloured, white and Indian adults self-selected for screening. Data collection included self-reported behavioural risk factors and clinical measurements comprising blood pressure, anthropometry and point-of-care random blood glucose and cholesterol assessments.ResultsAmong the 7711 participants, 2488 men and 5223 women, the prevalence of diabetes and hypertension increased by BMI category across population groups. Compared with white men and women, black African men (odds ratio: 2.66, 95% confidence interval: 1.70-4.16) and women (2.10, 1.49-2.96), coloured men (2.28, 1.44-3.60) and women (2.15, 1.52-3.05) and Indian men (4.38, 2.65-7.26) and women (3.64, 2.50-5.32) were significantly more likely to have diabetes. The odds for hypertension were significantly higher only in coloured men compared with white men (1.37, 1.02-1.83), while it was significantly higher in black African, coloured and Indian women compared with white women. The odds for hypercholesterolaemia were significantly lower in black African men (0.64, 0.49-0.84) and women (0.52, 0.43-0.62) compared with white men and women, and significantly higher in Indian men (1.47, 1.05-2.08) compared with white men. Black African women compared with their male counterparts were less likely to have diabetes (0.64, 0.46-0.89). Black African (0.66, 0.54-.082), coloured (0.65, 0.50-0.84) and white (0.69, 0.53-0.88) women were significantly less likely to have hypertension compared with their male counterparts. The odds for hypercholesterolaemia were higher in coloured (1.44, 1.16-1.80) and white (1.47, 1.18-1.84) women compared with their counterparts.ConclusionsThe cardio-metabolic diseases of diabetes, hypertension and hypercholesterolaemia were differentially associated with population groups and gender in South Africa. The insights obtained highlight the need for multi-disciplinary targeted management approaches in high-risk populations.

Project description:ObjectiveGamma-glutamyl dipeptides are bioactive peptides involved in inflammation, oxidative stress, and glucose regulation. Gamma-glutamyl-leucine (Gamma-Glu-Leu) has been extensively reported to be associated with the risk of cardio-metabolic diseases, such as obesity, metabolic syndrome, and type 2 diabetes. However, the causality remains to be uncovered. The aim of this study was to explore the causal-effect relationships between Gamma-Glu-Leu and metabolic risk.Materials and methodsIn this study, 1,289 subjects were included from a cross-sectional survey on metabolic syndrome (MetS) in eastern China. Serum Gamma-Glu-Leu levels were measured by untargeted metabolomics. Using linear regressions, a two-stage genome-wide association study (GWAS) for Gamma-Glu-Leu was conducted to seek its instrumental single nucleotide polymorphisms (SNPs). One-sample Mendelian randomization (MR) analyses were performed to evaluate the causality between Gamma-Glu-Leu and the metabolic risk.ResultsFour SNPs are associated with serum Gamma-Glu-Leu levels, including rs12476238, rs56146133, rs2479714, and rs12229654. Out of them, rs12476238 exhibits the strongest association (Beta = -0.38, S.E. = 0.07 in discovery stage, Beta = -0.29, S.E. = 0.14 in validation stage, combined P-value = 1.04 × 10-8). Each of the four SNPs has a nominal association with at least one metabolic risk factor. Both rs12229654 and rs56146133 are associated with body mass index, waist circumference (WC), the ratio of WC to hip circumference, blood pressure, and triglyceride (5 × 10-5 < P < 0.05). rs56146133 also has nominal associations with fasting insulin, glucose, and insulin resistance index (5 × 10-5 < P < 0.05). Using the four SNPs serving as the instrumental SNPs of Gamma-Glu-Leu, the MR analyses revealed that higher Gamma-Glu-Leu levels are causally associated with elevated risks of multiple cardio-metabolic factors except for high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (P > 0.05).ConclusionFour SNPs (rs12476238, rs56146133, rs2479714, and rs12229654) may regulate the levels of serum Gamma-Glu-Leu. Higher Gamma-Glu-Leu levels are causally linked to cardio-metabolic risks. Future prospective studies on Gamma-Glu-Leu are required to explain its role in metabolic disorders.

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Dataset Information

Associations of gamma-glutamyl transferase with cardio-metabolic diseases in people living with HIV infection in South Africa.

Background

Methods

Results

Conclusions

Publications

Associations of gamma-glutamyl transferase with cardio-metabolic diseases in people living with HIV infection in South Africa.

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