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Association of apolipoprotein E polymorphism with plasma lipid disorders, independent of obesity-related traits in Vietnamese children.

ABSTRACT: The dyslipidemia associated with obesity plays a major role in the development of atherosclerosis and cardiovascular disease. Dyslipidemia in childhood can progress in adult stage. APOE is one of the most important genes that regulate plasma lipid transport and clearance. The study aimed to assess whether the common APOE polymorphism is associated with lipid profiles and dyslipidemia, and it could be modulated by obesity-related traits (body mass index, waist circumference, hip circumference, and waist-to-hip ratio) in Vietnamese children.A case-control study was designed including 249 cases with dyslipidemia and 600 controls without dyslipidemia. Dyslipidemia is defined as elevated total or low-density lipoprotein (LDL) cholesterol levels, or low levels of high-density lipoprotein (HDL) cholesterol. Genotype for APOE polymorphism (rs7412 and rs429358) was determined by the polymerase chain reaction and restriction fragment length polymorphism method. The association of APOE genotypes with plasma lipid disorders was tested by binary logistic regression analysis, taking into account the confounding factors of age, sex, residence, province and obesity-related traits.In comparison with ?3/?3 carriers, the ?4 carriers had the highest concentration of serum TC and LDL-C in cases and controls (P???0.001), while ?2 carriers had the lowest. Carriers without TT haplotype had higher serum TC than those with TT haplotype. The ?4 carriers had higher hypoalphalipoproteinemia risk than ?3/?3 carriers (OR?=?2.78, P?=?0.02) before and after adjustment for age, gender, residence and obesity-related traits.The study suggested that the APOE genotype and haplotype significantly associated with plasma TC and LDL-C level in Vietnamese children. The association of APOE genotype with hypoalphalipoproteinemia was independent of obesity-related traits.

SUBMITTER: Hanh NT

PROVIDER: S-EPMC5057250 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Association of apolipoprotein E polymorphism with plasma lipid disorders, independent of obesity-related traits in Vietnamese children.

Hanh Nguyen Thi Hong NT Nhung Bui Thi BT Dao Duong Thi Anh DT Tuyet Le Thi LT Hop Le Thi LT Binh Tran Quang TQ Thuc Vu Thi Minh VT

Lipids in health and disease 20161010 1

<h4>Background</h4>The dyslipidemia associated with obesity plays a major role in the development of atherosclerosis and cardiovascular disease. Dyslipidemia in childhood can progress in adult stage. APOE is one of the most important genes that regulate plasma lipid transport and clearance. The study aimed to assess whether the common APOE polymorphism is associated with lipid profiles and dyslipidemia, and it could be modulated by obesity-related traits (body mass index, waist circumference, hi ...[more]

PMID: 27724906

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Project description:BackgroundSchistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein E (APOE) gene polymorphism, a known modulator of lipid metabolism, on plasma lipid levels in patients with hepatosplenic schistosomiasis.Methodology/principal findingsBlood samples were used for APOE genotyping and to measure total cholesterol (TC), LDL-C, HDL-C and triglycerides. Schistosomiasis patients had reduced TC, LDL-C and triglycerides (25%, 38% and 32% lower, respectively; P<0.0001) compared to control individuals, whereas HDL-C was increased (10% higher; P?=?0.0136). Frequency of the common alleles, ?2, ?3 and ?4, was similar (P?=?0.3568) between controls (n?=?108) and patients (n?=?84), implying that APOE genotype did not affect susceptibility to the advanced stage of schistosomiasis. Nevertheless, while patient TC and LDL-C levels were significantly reduced for each allele (except TC in ?2 patients), changes in HDL-C and triglycerides were noted only for the less common ?2 and ?4 alleles. The most striking finding, however, was that accepted regulation of plasma lipid levels by APOE genotype was disrupted by schistosomiasis. Thus, while ?2 controls had higher TC and LDL-C than ?3 carriers, these parameters were lower in ?2 versus ?3 patients. Similarly, the inverse relationship of TG levels in controls (?2>?3>?4) was absent in patients (?2 or ?4>?3), and the increase in HDL-C of ?2 or ?4 patients compared to ?3 patients was not seen in the control groups.Conclusion/significanceWe confirm that human schistosomiasis causes dyslipidemia and report for the first time that certain changes in plasma lipid and lipoprotein levels depend on APOE gene polymorphism. Importantly, we also concluded that S. mansoni disrupts the expected regulation of plasma lipids by the different ApoE isoforms. This finding suggests ways to identify new metabolic pathways affected by schistosomiasis and also potential molecular targets to treat associated morbidities.

Project description:BackgroundThe interaction between apolipoprotein A-II (APOA2) m265 genotype and saturated fat for obesity traits has been more extensively demonstrated than for any other locus, but behavioural and hormonal mechanisms underlying this relationship are unexplored. In this study, we evaluated relationships between APOA2 and obesity risk with particular focus on patterns of eating and ghrelin, a hormonal regulator of food intake.DesignCross-sectional study.SubjectsOverweight and obese subjects (n=1225) were evaluated at baseline in five weight loss clinics in southeastern Spain.MethodsBehavioural data were assessed using a checklist of weight loss obstacles. Logistic regression models were fitted to estimate the risk of a specific behaviour associated with APOA2 genotype. Relationships between APOA2 genotype and saturated fat intakes for anthropometric traits and plasma ghrelin were evaluated by analysis of variance. To construct categorical variables to evaluate interactions, saturated fat intake was dichotomized into high and low according to the population median intake or as tertiles.ResultsHomozygous minor (CC) subjects were more likely to exhibit behaviours that impede weight loss ('Do you skip meals', odds ratio (OR)=2.09, P=0.008) and less likely to exhibit the protective behaviour of 'Do you plan meals in advance' (OR=0.64, P=0.034). Plasma ghrelin for CC subjects consuming low saturated fat was lower compared with (1) CC subjects consuming high saturated fat, (2) TT+TC carriers consuming low saturated fat and (3) TT+TC carriers consuming high saturated fat (all P<0.05).ConclusionsAPOA2 m265 genotype may be associated with eating behaviours and dietary modulation of plasma ghrelin. Expansion of knowledge of APOA2 and obesity to include modulation of specific behaviours and hormonal mediators not only broadens understanding of gene-diet interactions, but also facilitates the pragmatic, future goal of developing dietary guidelines based on genotype.

Project description: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.

Dataset Information

Association of apolipoprotein E polymorphism with plasma lipid disorders, independent of obesity-related traits in Vietnamese children.

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Association of apolipoprotein E polymorphism with plasma lipid disorders, independent of obesity-related traits in Vietnamese children.

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