Dataset Information

Associations Between Apolipoprotein-A5 Genotype, High-Fat Diet and Plasma Lipid Levels among HIV-infected Children Initiating Antiretroviral Therapy in India

ABSTRACT: Abstract

Background

Both antiretroviral therapy (ART) and polymorphism in genes involved in lipoprotein metabolism contribute to the development of ART-induced dyslipidemia. Apolipoprotein A5 (APOA5)gene variant, which vary by race/ethnicity, influence plasma lipid concentrations. We explored the association of candidate gene effect on plasma lipid levels with food in HIV-infected children initiating ART in south India.

Methods

HIV-infected children, between 2 and 12 years of age initiating non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART during 2010–2014 were included. They were assessed for their dietary intake by 24-hour dietary recall. Fasting blood was drawn for serum triglycerides (TGL), total cholesterol and high-density cholesterol along with CD4 cell count, and HIV-1 viral load. APOA5 gene polymorphisms rs662799, rs3135506 were determined by Taqman single-nucleotide polymorphism (SNP) genotyping assays. The General Linear Model (GLM) was applied to explore the risk of hypertriglyceridemia for SNP’s rs662799 and rs3135506 with food interaction in children.

Results

Three hundred and ninety HIV-infected children {median age (IQR): 9 (5–11) years; and median viral load: 141,000 (25,876–436,000) copies/mL} were started on NNRTI-based ART. The frequency of c allele was 20% and 3.0% in rs662799, rs3135506, respectively. The GLM model suggested that the SNP rs662799 has significant association with TGL(P < 0.01); there was, however no interaction between gene polymorphisms and food. Also, the prediction model revealed that those who had a carrier allele (C) had higher TGL level as compared with those with wild type (165 vs. 138 mg/dL) and girls had higher TGL levels compared with boys.

Conclusion

Children with carrier allele of APOA5 are prone to hypertriglyceridemia, irrespective of diet or drugs. These children require periodic monitoring of lipid parameters and effective interventions to prevent the development of atherogenic or metabolic complications.

Disclosures

All authors: No reported disclosures.

SUBMITTER: Srinivasan R

PROVIDER: S-EPMC5631611 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundApolipoprotein E (APOE) polymorphism is associated with lipid levels. Some studies have reported that blood lipid response to diet or obesity varies depending on APOE genotypes. The aim of this study was to assess the effect of APOE genotypes, the intake of saturated fatty acids (SFA), and obesity on serum lipid levels in Lithuanian adult population.Methodology/principal findingsA cross-sectional health survey was carried out in five municipalities of Lithuania. The random sample was obtained from lists of 25-64 year-old inhabitants registered at primary health care centres. The data from 996 subjects (416 men and 580 women) were analysed in this study. Two single-nucleotide polymorphisms (rs429358 and rs7412) were assessed using a real-time polymerase chain reaction. 24-hour recall and food frequency questionnaire were used for evaluation of dietary habits. Serum lipids were determined using enzymatic methods. Men and women with the APOE2 genotype had the lowest level of total cholesterol (TC) (p = 0.002 for men, and p = 0.02 for women) and low-density lipoprotein cholesterol (LDL-C) (p<0.001). Multivariate linear regression analysis showed that age, genotype APOE2, SFA intake, and body mass index (BMI) were significant determinants of TC and LDL-C level (with p values ranging from 0.043 to 0.001). Our data did not reveal any statistically significant interactions between APOE genotype and SFA intake or between APOE genotype and BMI regarding TC and LDL-C level (all p>0.05). However, the predictive power of the regression model for LDL-C improved when gene-BMI interaction and gene-BMI interaction plus gene-nutrient interaction were added (p = 0.04 and p = 0.032 for R(2) change, respectively).Conclusions/significanceAPOE genotypes, SFA intake, and obesity were found to be associated with blood lipid levels in Lithuanian adult population. Analysis of gene-diet and gene-obesity interactions did not confirm that the effects of diet and obesity on TC and LDL-C level significantly depended on APOE genotype.

Project description:IntroductionAdverse drug reactions related to antiretroviral therapy (ART) remain a challenge in resource-limited settings, often causing significant morbidity and impaired adherence leading to treatment failure. This 2-year prospective study aimed to describe patterns and predictors of adverse reactions to first-line ART and assess the impact of these events on treatment success.MethodsBetween 2010-2013, 321 ART-naïve eligible adults were enrolled at two clinics in southern India. ART regimens included zidovudine or stavudine plus lamivudine, plus nevirapine or efavirenz. Pill count adherence, immunological and virological monitoring, and laboratory-based adverse drug reactions were measured prospectively and analyzed.ResultsAmong 321 patients in the study, 289 (90.0%) patients experienced at least 1 adverse reaction, and 85 (26.5%) experienced at least 1 severe reaction. The incidence rate was 52 and 15 per 100 person-years for all reactions and severe reactions respectively. The cumulative incidence of zidovudine-induced anemia was 37.1% over 2 years. At 12 and 24 months, the proportion of patients with optimal adherence, undetectable viral load and CD4 counts >350 cells/mm3 were similar between patients who experienced or did not experience severe adverse drug reactions.ConclusionsOur results highlight the high frequency of ART-related adverse drug reactions among individuals initiating first-line ART in India, underscoring the importance of detailed counseling and monitoring for maintaining ART durability. Severe drug-induced anemia needs to be addressed urgently with alternative first-line agents, and close laboratory surveillance. High treatment efficacy despite decreased drug safety seen here may be because patients have limited treatment options. Our results support the use of currently recommended safer first-line ART regimens that minimize the risk of severe life-threatening toxicities and provide for a better quality of life.Trial registrationISRTCN Registry: ISRCTN79261738.

Project description:BACKGROUND:Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART). METHODS:In the Women's Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness was measured by B-mode ultrasound. RESULTS:Relative to HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-? (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P < 0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemoattractant protein 1 (190 vs 163 pg/mL, P < 0.0001), and D-dimer (0.43 vs 0.31 ?g/mL, P < 0.01). Elevated biomarker levels declined after HAART. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-? levels remained elevated compared with HIV-uninfected women (+0.8 pg/mL, P = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P = 0.05), and D-dimer (P = 0.03) were associated with increased carotid artery intima-media thickness. CONCLUSIONS:Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-?), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy.

Project description:BackgroundThere is conflicting evidence on the immunologic benefit of treating helminth co-infections ("deworming") in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART.Methodology/principal findingsTo estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (? = 42.8; 95% CI, -2.1 to 87.7) or after the first year of ART (? = ?-9.9; 95% CI, -24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (? = 63.0; 95% CI, 6.0 to 120.1) in females.Conclusions/significanceEmpiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART-naïve individuals, but suggest that certain sub-populations may benefit.

Project description:Sporadic Alzheimer disease (AD) is caused in part by decreased clearance of the ?-amyloid (A?) peptide breakdown products. Lipid-depleted (LD) apolipoproteins are less effective at binding and clearing A?, and LD A? peptides are more toxic to neurons. However, not much is known about the lipid states of these proteins in human cerebrospinal fluid.To characterize the lipidation states of A? peptides and apolipoprotein E in the cerebrospinal fluid in adults with respect to cognitive diagnosis and APOE ?4 allele carrier status and after a dietary intervention.Randomized clinical trial.Veterans Affairs Medical Center clinical research unit.Twenty older adults with normal cognition (mean [SD] age, 69 [7] years) and 27 with amnestic mild cognitive impairment (67 [6] years).Randomization to a diet high in saturated fat content and with a high glycemic index (High diet; 45% of energy from fat [>25% saturated fat], 35%-40% from carbohydrates with a mean glycemic index >70, and 15%-20% from protein) or a diet low in saturated fat content and with a low glycemic index (Low diet; 25% of energy from fat [<7% saturated fat], 55%-60% from carbohydrates with a mean glycemic index <55, and 15%-20% from protein).Lipid-depleted A?42 and A?40 and apolipoprotein E in cerebrospinal fluid.Baseline levels of LD A? were greater for adults with mild cognitive impairment compared with adults with normal cognition (LD A?42, P = .05; LD A?40, P = .01). These findings were magnified in adults with mild cognitive impairment and the ?4 allele, who had higher LD apolipoprotein E levels irrespective of cognitive diagnosis (P < .001). The Low diet tended to decrease LD A? levels, whereas the High diet increased these fractions (LD A?42, P = .01; LD A?40, P = .15). Changes in LD A? levels with the Low diet negatively correlated with changes in cerebrospinal fluid levels of insulin (LD A?42 and insulin, r = -0.68 [P = .01]; LD A?40 and insulin, r = -0.78 [P = .002]).The lipidation states of apolipoproteins and A? peptides in the brain differ depending on APOE genotype and cognitive diagnosis. Concentrations can be modulated by diet. These findings may provide insight into the mechanisms through which apolipoprotein E4 and unhealthy diets impart risk for developing AD.

Project description:The association of single nucleotide polymorphisms (SNPs) in the apolipoprotein (Apo) A1/C3/A4/A5 gene cluster and serum lipid profiles is inconsistent. The present study was undertaken to detect the association between the ApoA1/C3/A5 gene polymorphisms and their haplotypes with serum lipid levels in the general Chinese population.A total of 1030 unrelated subjects (492 males and 538 females) aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoA1 -75 bp G>A, ApoC3 3238C>G, ApoA5 -1131T>C, ApoA5 c.553G>T and ApoA5 c.457G>A was performed by polymerse chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Pair-wise linkage disequilibria and haplotype analysis among the five SNPs were estimated.The levels of high-density lipoprotein cholesterol (HDL-C) and ApoA1 were lower in males than in femailes (P < 0.05 for each). The allelic and genotypic frequencies of the SNPs were no significant difference between males and females except ApoC3 3238C>G. There were 11 haplotypes with a frequency >1% identified in the cluster in our population. At the global level, the haplotypes comprised of all five SNPs were significantly associated with all seven lipid traits. In particular, haplotype G-G-C-C-A (6%; in the order of ApoA5 c.553G>T, ApoA5 c.457G>A, ApoA5 -1131T>C, ApoC3 3238C>G, and ApoA1 -75bp G>A) and G-A-T-C-G (4%) showed consistent association with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ApoA1, ApoB, and the ApoA1/ApoB ratio. In addition, carriers of haplotype G-G-T-C-G (26%) had increased serum concentration of HDL-C and ApoA1, whereas carriers of G-G-C-G-G (15%) had high concentrations of TC, triglyceride (TG) and ApoB. We also found that haplotypes with five SNPs explain much more serum lipid variation than any single SNP alone, especially for TG (4.4% for haplotype vs. 2.4% for -1131T>C max based on R-square) and HDL-C (5.1% for haplotype vs. 0.9% for c.553G>T based on R-square). Serum lipid parameters were also correlated with genotypes and several environment factors.Several common SNPs and their haplotypes in the ApoA1/C3/A5 gene cluster are closely associated with modifications of serum lipid parameters in the general Chinese population.