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Genetic markers associated to dyslipidemia in HIV-infected individuals on HAART.

ABSTRACT: This study evaluated the impact of 9 single nucleotide polymorphisms (SNPs) in 6 candidate genes (APOB, APOA5, APOE, APOC3, SCAP, and LDLR) over dyslipidemia in HIV-infected patients on stable antiretroviral therapy (ART) with undetectable viral loads. Blood samples were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas, and Rio Grande in Brazil. The SNPs were genotyped by conventional polymerase chain reaction (PCR) and real-time PCR. The prevalence of dyslipidemia was particularly high among the protease inhibitors-treated patients (79%). APOE (rs429358 and rs7412) genotypes and APOA5 -1131T>C (rs662799) were associated with plasma triglycerides (TG) and low-density-lipoprotein cholesterol levels (LDL-C). The APOA5 -1131T>C (rs662799) and SCAP 2386A>G (rs12487736) polymorphisms were significantly associated with high-density-lipoprotein cholesterol levels. The mean values of the total cholesterol and LDL-C levels were associated with both the APOB SP Ins/Del (rs17240441) and APOB XbaI (rs693) polymorphisms. In conclusion, our data support the importance of genetic factors in the determination of lipid levels in HIV-infected individuals. Due to the relatively high number of carriers of these risk variants, studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen.

SUBMITTER: Lazzaretti RK

PROVIDER: S-EPMC3804371 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Genetic markers associated to dyslipidemia in HIV-infected individuals on HAART.

Lazzaretti Rosmeri K RK Gasparotto Aline S AS Sassi Marina G de M MG Polanczyk Carísi A CA Kuhmmer Regina R Silveira Jussara M JM Basso Rossana P RP Pinheiro Cezar A T CA Silveira Mariângela F MF Sprinz Eduardo E Mattevi Vanessa S VS

TheScientificWorldJournal 20130926

This study evaluated the impact of 9 single nucleotide polymorphisms (SNPs) in 6 candidate genes (APOB, APOA5, APOE, APOC3, SCAP, and LDLR) over dyslipidemia in HIV-infected patients on stable antiretroviral therapy (ART) with undetectable viral loads. Blood samples were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas, and Rio Grande in Brazil. The SNPs were genotyped by conventional polymerase chain reaction (PCR) and real-time PCR. The prevalence of dys ...[more]

PMID: 24191141

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Project description:BackgroundThough the initiation of Highly Active Antiretroviral Therapy (HAART) has led to decreased HIV/AIDS related mortality, the regimen has been reported to be associated with lipid toxicities. Baseline data on such disturbances are required to induce countrywide interventional HIV/AIDS programs. The aim of this study was to determine the frequency and risks of dyslipidemia in HIV patients on HAART medication in Eritrea.MethodsA cross sectional study was conducted on HIV/AIDS patients in two national referral hospitals in Asmara, Eritrea. A structured questionnaire was used to collect demographic data and blood sample was taken for analyses of lipid profile tests. Data was analyzed using chi-square test, Post Hoc and logistic regression in SPSS software.ResultsThe study included 382 participants of whom 256(67%) were females. Their median age, CD4+ T cell count (cell/microliter) and duration of HAART (years) was 45(IQR: 38-51), 434(IQR: 294-583) & 5(IQR: 3-5) respectively. The prevalence of dyslipidemia was 331(86.6%). Increased Low Density Lipoprotein-C (LDL-C) 213(55.8%) was the predominant abnormality. Abacavir was significantly related with highest means of triglycerides (TG) (228.17 ± 193.81) and lowest means of High Density Lipoprotein (HDL-C) (46.94 ± 12.02). Females had substantially higher proportions of TG (aOR = 2.89, 95% CI: 1.65-5.05) and TC/HDL ratio (aOR = 2.33, 95% CI: 1.40-3.87) and low HDL-C (aOR = 2.16, 95% CI: 1.34-3.48). Increased age was related with increased pro-atherogenic lipid parameters. High LDL-C was more infrequent in non-smokers (aOR = 0.028, 95% CI: 0.12-0.69).ConclusionThe study showed a high prevalence of dyslipidemia in HIV-patients receiving HAART in Eritrea. Sex, age and smoking practice were among key factors associated with dyslipidemia. The necessity to assess lipid profiles and other cardiovascular risk factors before initiation of HAART treatment and continuous monitoring during therapy is mandatory.

Project description:BackgroundAlthough gut microbiota dysbiosis has been reported in HIV infected individuals recently, the relationship between the gut microbiota and immune activation in patients with different immune responses to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (healthy controls) and 58 HIV-infected individuals, including 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and < 200 CD4+ T-cell counts/μl after 2 years of HIV-1 viral suppression respectively) without comorbidities.ResultsMetagenome sequencing revealed that HIV-infected immunological responders and immunological non-responders could not recover completely from the gut microbiota dysbiosis. At a 97% similarity level, the relative abundances of Fusobacterium, Ruminococcus gnavus and Megamonas were greater, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacterium rectale and Roseburia were more depleted in the IR and INR groups than those in the healthy controls. Ruminococcaceae and Alistipes were positively correlated with nadir and current CD4+ T-cell counts, but negatively correlated with CD8 + CD57+ T-cell counts. Inflammation markers and translocation biomarkers (LPS) levels were positively correlated with the abundances of genera Ruminococcus and Fusobacterium but were negatively correlated with the genus Faecalibacterium. The relative abundances of Escherichia-Shigella and Blautia were significantly higher in the IR than those in the INR group. Escherichia-Shigella were negatively correlated with the CD4/CD8 ratio but positively correlated with the amount of CD8 + CD57+ T-cells. Roseburia and Blautia were negatively associated with nadir CD4+ T-cell and positively associated with CD8 + CD57+ T-cell counts.ConclusionsGut microbiota dysbiosis may be one of the factors contributing to different immune responses and treatment outcomes to HAART.

Project description:Highly active antiretroviral therapy (HAART) is known to cause lipid abnormalities such as dyslipidaemia in HIV-infected individuals. Yet, dyslipidaemia may not independently occur as it may be worsened by single nucleotide polymorphisms (SNPs) in lecithin cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL). This case-control study was conducted in three-selected hospitals in the Northern part of Ghana. The study constituted a total of 118 HIV-infected participants aged 19-71 years, who had been on HAART for 6-24 months. Dyslipidaemia was defined based on the NCEP-ATP III criteria. HIV-infected individuals on HAART with dyslipidaemia were classified as cases while those without dyslipidaemia were grouped as controls. Lipid profile was measured using an automatic clinical chemistry analyzer and genomic DNA was extracted for PCR (GeneAmp PCR System 2700). Overall, the prevalence of dyslipidaemia was 39.0% (46/118). High levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and reduced levels of high-density lipoprotein cholesterol (HDL-C) were observed in all cases. A total of 256 selected PCR amplicons comprising 137 LPL (exons 3, 5 and 6) and 119 LCAT (exons 1, 4, and 6) were sequenced in 46 samples (Inqaba Biotech). Six (6) clinically significant SNPs were identified in exons 1 and 4 for LCAT whereas 25 non-clinically significant SNPs were identified for LPL in exons 5 and 6. At position 97 for LCAT exon 1, there was a deletion of the nucleotide, 'A' in 32.5% (13/40) of the sampled population while 67.5% (27/40) of the sample population retained the nucleotide, 'A' which was significantly associated with dyslipidaemic outcomes in the study population (p = 0.0004). A total of 25 SNPs were identified in exons 5 and 6 of LPL; 22 were substitutions, and 3 were insertions. However, none of the 25 SNPs identified in LPL exon 5 and 6 were statistically significant. SNPs in LCAT may independently contribute to dyslipidaemia among Ghanaian HIV-infected individuals on HAART, thus, allowing genetic and/or functional differential diagnosis of dyslipidaemia and creating an opportunity for potentially preventive options.

Project description:Co-infection with hepatitis B (HBV) and human immunodeficiency virus (HIV) increases overall and liver-related mortality. In order to identify interactions between these two viruses in vivo, full-length HIV proviruses were sequenced from a cohort of HIV-HBV co-infected participants and from a cohort of HIV mono-infected participants recruited from Bangkok, Thailand, both before the initiation of antiretroviral therapy (ART) and after at least 2 years of ART. The co-infected individuals were found to have higher levels of genetically-intact HIV proviruses than did mono-infected individuals pre-therapy. In these co-infected individuals, higher levels of genetically-intact HIV proviruses or proviral genetic-diversity were also associated with higher levels of sCD14 and CXCL10, suggesting that immune activation is linked to more genetically-intact HIV proviruses. Three years of ART decreased the overall level of HIV proviruses, with fewer genetically-intact proviruses being identified in co-infected versus mono-infected individuals. However, ART increased the frequency of certain genetic defects within proviruses and the expansion of identical HIV sequences. IMPORTANCE With the increased availability and efficacy of ART, co-morbidities are now one of the leading causes of death in HIV-positive individuals. One of these co-morbidities is co-infection with HBV. However, co-infections are still relatively understudied, especially in countries where such co-infections are endemic. Furthermore, these countries have different subtypes of HIV circulating than the commonly studied HIV subtype B. We believe that our study serves this understudied niche and provides a novel approach to investigating the impact of HBV co-infection on HIV infection. We examine co-infection at the molecular level in order to investigate indirect associations between the two viruses through their interactions with the immune system. We demonstrate that increased immune inflammation and activation in HBV co-infected individuals is associated with higher HIV viremia and an increased number of genetically-intact HIV proviruses in peripheral blood cells. This leads us to hypothesize that inflammation could be a driver in the increased mortality rate of HIV-HBV co-infected individuals.

Dataset Information

Genetic markers associated to dyslipidemia in HIV-infected individuals on HAART.

Publications

Genetic markers associated to dyslipidemia in HIV-infected individuals on HAART.

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