APOA4 Polymorphism as a Risk Factor for Unfavorable Lipid Serum Profile and Depression: A Cross-Sectional Study

Ota, Vanessa Kiyomi; Chen, Elizabeth; Ejchel, Tatiana Flank; Furuya, Tatiane Katsue; Mazzotti, Diego R.; Cendoroglo, Maysa Seabra; Ramos, Luiz Roberto; Araújo, Lara Quirino; Burbano, Rommel Rodrı́guez; Smith, Marı́lia de Arruda Cardoso

doi:10.2310/jim.0b013e31822467cd

Cited by 25 publications

(7 citation statements)

References 41 publications

(67 reference statements)

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“… 16 APOA4 polymorphism has been reported as a risk factor for an unfavorable lipid serum profile. 17 On the other hand, a growing body of evidence suggests that obesity, hypertriglyceridemia, and reduced high-density lipoprotein cholesterol (HDL-c) is important in the development of cognitive impairment and AD. APOA1 was also observed at lower levels in AD patients via proteomic two-dimensional gel electrophoresis in 2006.…”

Section: Introductionmentioning

confidence: 99%

Decreased expression of the APOA1–APOC3–APOA4 gene cluster is associated with risk of Alzheimer’s disease

Lin¹,

Cao²,

Gao³

2015

DDDT

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BackgroundApolipoprotein is genetically associated with the risk of Alzheimer’s disease (AD). The APOA1, APOC3, and APOA4 genes are closely linked and located on human chromosome 11. Therefore, this gene cluster may be related to the risk of AD.Patients and methodsA total of 147 AD patients and 160 healthy controls were randomly recruited from June 2013 to August 2014. APOA1, APOC3, and APOA4 levels were measured using real-time quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay.ResultsAPOA1, APOC3 and APOA4 levels were significantly lower in AD patients than controls (P<0.01). APOA1, APOC3, and APOA4 levels were negatively related with the severities of AD determined by Clinical Dementia Rating scores (P<0.01). APOA1, APOC3, and APOA4 levels showed a negative relation with Montgomery–Åsberg Depression Rating Scale scores and a positive relation with RAND 36-item health-survey scores (P<0.01). There was a decreased trend for levels of APOA1, APOC3, and APOA4 in AD patients.ConclusionLow levels of APOA1, APOC3, and APOA4 are associated with risk of AD. APOA1, APOC3, and APOA4 should be developed as combined drugs for the therapy of AD.

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Section: Introductionmentioning

confidence: 99%

Decreased expression of the APOA1–APOC3–APOA4 gene cluster is associated with risk of Alzheimer’s disease

Lin¹,

Cao²,

Gao³

2015

DDDT

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“…Small interfering RNA knockdown of Sort1 in the mouse was shown to alter plasma LDL, indicating that this is likely the causal gene in this gene cluster (Musunuru et al, 2010). ZNF259 is adjacent to APOA5, APOA4, APOC3, APOA1, and BUD13, all of which have been previously associated with differences in circulating plasma lipids (Pollin et al, 2008; Teslovich et al, 2010; Ota et al, 2011; Global Lipids Genetics Consortium, 2013; Aung et al, 2014). These genes are in high linkage disequilibrium, and although functional studies have demonstrated a clear role for apolipoprotein genes in regulating lipids (Ito et al, 1990; Rubin et al, 1991; Pennacchio & Rubin, 2003), additional studies are needed to fully understand how these genes influence disease.…”

Section: Discussionmentioning

confidence: 86%

Common and rare genetic markers of lipid variation in subjects with type 2 diabetes from the ACCORD clinical trial

Marvel

Rotroff

Wagner

et al. 2017

PeerJ

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BackgroundIndividuals with type 2 diabetes are at an increased risk of cardiovascular disease. Alterations in circulating lipid levels, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) are heritable risk factors for cardiovascular disease. Here we conduct a genome-wide association study (GWAS) of common and rare variants to investigate associations with baseline lipid levels in 7,844 individuals with type 2 diabetes from the ACCORD clinical trial.MethodsDNA extracted from stored blood samples from ACCORD participants were genotyped using the Affymetrix Axiom Biobank 1 Genotyping Array. After quality control and genotype imputation, association of common genetic variants (CV), defined as minor allele frequency (MAF) ≥ 3%, with baseline levels of TC, LDL, HDL, and TG was tested using a linear model. Rare variant (RV) associations (MAF < 3%) were conducted using a suite of methods that collapse multiple RV within individual genes.ResultsMany statistically significant CV (p < 1 × 10−8) replicate findings in large meta-analyses in non-diabetic subjects. RV analyses also confirmed findings in other studies, whereas significant RV associations with CNOT2, HPN-AS1, and SIRPD appear to be novel (q < 0.1).DiscussionHere we present findings for the largest GWAS of lipid levels in people with type 2 diabetes to date. We identified 17 statistically significant (p < 1 × 10−8) associations of CV with lipid levels in 11 genes or chromosomal regions, all of which were previously identified in meta-analyses of mostly non-diabetic cohorts. We also identified 13 associations in 11 genes based on RV, several of which represent novel findings.

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“…33 Loss of appetite and thirst is one of the fundamental characteristics of chronic fatigue, and thus the differential expression of ApoA-IV represents a highly relevant finding. A polymorphism of the APOA4 gene is associated with depression, 34 and upregulation of APOA4 gene expression was significantly associated with poststroke depression. 35 In addition, in a recent plasma proteomic study of late-life depression, ApoA-IV protein was one of a panel of three proteins that could discriminate depressive from non-depressive elderly subjects.…”

Section: Discussionmentioning

confidence: 99%

Fatigue in primary Sjögren’s syndrome: A proteomic pilot study of cerebrospinal fluid

et al. 2019

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Objectives: Fatigue is a frequent and often disabling phenomenon that occurs in patients with chronic inflammatory and immunological diseases, and the underlying biological mechanisms are largely unknown. Because fatigue is generated in the brain, we aimed to investigate cerebrospinal fluid and search for molecules that participate in the pathophysiology of fatigue processes. Methods: A label-free shotgun proteomics approach was applied to analyze the cerebrospinal fluid proteome of 20 patients with primary Sjögren’s syndrome. Fatigue was measured with the fatigue visual analog scale. Results: A total of 828 proteins were identified and the 15 top discriminatory proteins between patients with high and low fatigue were selected. Among these were apolipoprotein A4, hemopexin, pigment epithelium-derived factor, secretogranin-1, secretogranin-3, selenium-binding protein 1, and complement factor B. Conclusion: Most of the discriminatory proteins have important roles in regulation of innate immunity, cellular stress defense, and/or functions in the central nervous system. These proteins and their interacting protein networks may therefore have central roles in the generation and regulation of fatigue, and the findings contribute with evidence to the concept of fatigue as a biological phenomenon signaled through specific molecular pathways.

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APOA4 Polymorphism as a Risk Factor for Unfavorable Lipid Serum Profile and Depression: A Cross-Sectional Study

Abstract: Our data suggest that 360His allele might be a risk factor for depression and unfavorable lipid profile and depression for elderly people in the Brazilian population.

Cited by 25 publications

References 41 publications

Decreased expression of the APOA1–APOC3–APOA4 gene cluster is associated with risk of Alzheimer’s disease

Decreased expression of the APOA1–APOC3–APOA4 gene cluster is associated with risk of Alzheimer’s disease

Common and rare genetic markers of lipid variation in subjects with type 2 diabetes from the ACCORD clinical trial

Fatigue in primary Sjögren’s syndrome: A proteomic pilot study of cerebrospinal fluid

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APOA4 Polymorphism as a Risk Factor for Unfavorable Lipid Serum Profile and Depression: A Cross-Sectional Study

Abstract: Our data suggest that 360His allele might be a risk factor for depression and unfavorable lipid profile and depression for elderly people in the Brazilian population.

Cited by 25 publications

References 41 publications

Decreased expression of the APOA1&ndash;APOC3&ndash;APOA4 gene cluster is associated with risk of Alzheimer&rsquo;s disease

Decreased expression of the APOA1&ndash;APOC3&ndash;APOA4 gene cluster is associated with risk of Alzheimer&rsquo;s disease

Common and rare genetic markers of lipid variation in subjects with type 2 diabetes from the ACCORD clinical trial

Fatigue in primary Sjögren’s syndrome: A proteomic pilot study of cerebrospinal fluid

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Product

Resources

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Decreased expression of the APOA1–APOC3–APOA4 gene cluster is associated with risk of Alzheimer’s disease

Decreased expression of the APOA1–APOC3–APOA4 gene cluster is associated with risk of Alzheimer’s disease