Plasma lipid transfer proteins: The role of PLTP and CETP in atherogenesis

Chowaniec, Zbyszko; Skoczyńska, Anna

doi:10.17219/acem/67968

Cited by 33 publications

(24 citation statements)

References 45 publications

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“…Reduced plasma PLTP activity was shown to cause markedly decreased HDL levels 34,35 . It also plays a role in inflammatory processes and participates in the etiology of atherosclerosis 36,37 . Remarkably, increased PLTP levels in plasma were identified as potential biomarker for AMD in a proteomics-based approach 38 .…”

Section: Discussionmentioning

confidence: 99%

A transcriptome-wide association study based on 27 tissues identifies 106 genes potentially relevant for disease pathology in age-related macular degeneration

Strunz

Kiel

et al. 2020

Sci Rep

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Genome-wide association studies (GWAS) for late stage age-related macular degeneration (AMD) have identified 52 independent genetic variants with genome-wide significance at 34 genomic loci. Typically, such an approach rarely results in the identification of functional variants implicating a defined gene in the disease process. We now performed a transcriptome-wide association study (TWAS) allowing the prediction of effects of AMD-associated genetic variants on gene expression. The TWAS was based on the genotypes of 16,144 late-stage AMD cases and 17,832 healthy controls, and gene expression was imputed for 27 different human tissues which were obtained from 134 to 421 individuals. A linear regression model including each individuals imputed gene expression data and the respective AMD status identified 106 genes significantly associated to AMD variants in at least one tissue (Q-value < 0.001). Gene enrichment analysis highlighted rather systemic than tissue-or cellspecific processes. Remarkably, 31 of the 106 genes overlapped with significant GWAS signals of other complex traits and diseases, such as neurological or autoimmune conditions. Taken together, our study highlights the fact that expression of genes associated with AMD is not restricted to retinal tissue as could be expected for an eye disease of the posterior pole, but instead is rather ubiquitous suggesting processes underlying AMD pathology to be of systemic nature. Age-related macular degeneration (AMD) is a frequent disease of the choroid, Bruch's membrane, retinal pigment epithelium and photoreceptor complex characterized by a progressive loss of vision in older individuals of industrialized countries. For the year 2016, it was estimated that worldwide approximately 162 million were affected by early AMD (prevalence 8.0%) and 10 million people by late AMD (prevalence 0.4%). These numbers were predicted to increase to 260 million patients with early and 19 million with late AMD by the year 2040 1. It is well established that AMD is a complex disease, involving environmental and genetic risk factors. The International AMD Genomics Consortium (IAMDGC) performed a genome-wide association study (GWAS) and reported 7,218 genetic variants to be associated with late-stage AMD at a genome-wide significance level (P-value ≤ 5 × 10 −8). Sequential forward selection finally identified 52 independent association signals, which are distributed over 34 genomic loci 2. An additional 11,768 variants (P-value ≤ 5 × 10 −4) failed to reach genome-wide significance in this study but may well play a role in AMD pathogenesis. These variants may become relevant only with an increase in sample-size in future GWAS, or by gathering additional information on the functional impact of these variants in relation to AMD pathology.

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Section: Discussionmentioning

confidence: 99%

A transcriptome-wide association study based on 27 tissues identifies 106 genes potentially relevant for disease pathology in age-related macular degeneration

Strunz

Kiel

et al. 2020

Sci Rep

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“…PLTP promotes cholesterol efflux and reverses cholesterol transfer [41], and is essential for maintaining normal HDL levels. PLTP correlated positively to apoA-I and negatively to apoB/apoA-I ratio.…”

Section: Discussionmentioning

confidence: 99%

Modified lipoproteins in periodontitis: a link to cardiovascular disease?

et al. 2019

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There is a strong association between periodontal disease and atherosclerotic cardiovascular disorders. A key event in the development of atherosclerosis is accumulation of modified lipoproteins within the arterial wall. We hypothesise that patients with periodontitis have an altered lipoprotein profile towards an atherogenic form. Therefore, the present study aims at identifying modifications of plasma lipoproteins in periodontitis. Lipoproteins from ten female patients with periodontitis and gender- and age-matched healthy controls were isolated by density-gradient ultracentrifugation. Proteins were separated by 2D gel-electrophoresis and identified by map-matching or by nano-LC followed by MS. Apolipoprotein (Apo) A-I (ApoA-I) methionine oxidation, Oxyblot, total antioxidant capacity and a multiplex of 71 inflammation-related plasma proteins were assessed. Reduced levels of apoJ, phospholipid transfer protein, apoF, complement C3, paraoxonase 3 and increased levels of α-1-antichymotrypsin, apoA-II, apoC-III were found in high-density lipoprotein (HDL) from the patients. In low-density lipoprotein (LDL)/very LDL (VLDL), the levels of apoL-1 and platelet-activating factor acetylhydrolase (PAF-AH) as well as apo-B fragments were increased. Methionine oxidation of apoA-I was increased in HDL and showed a relationship with periodontal parameters. α-1 antitrypsin and α-2-HS glycoprotein were oxidised in LDL/VLDL and antioxidant capacity was increased in the patient group. A total of 17 inflammation-related proteins were important for group separation with the highest discriminating proteins identified as IL-21, Fractalkine, IL-17F, IL-7, IL-1RA and IL-2. Patients with periodontitis have an altered plasma lipoprotein profile, defined by altered protein levels as well as post-translational and other structural modifications towards an atherogenic form, which supports a role of modified plasma lipoproteins as central in the link between periodontal and cardiovascular disease (CVD).

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“…PLUNC proteins are predominantly expressed in the upper airways and have host‐protective and immunomodulatory functions in response to inflammation (Britto & Cohn, ; Sayeed, Nistico, St Croix, & Di, ). CETP and PLTP are human plasma proteins and both play a major role in lipoprotein metabolism (Chowaniec & Skoczynska, ). However, less is known about the functionality of BPIFC protein.…”

Section: Discussionmentioning

confidence: 99%

Novel heterozygous BPIFC variant in a Chinese pedigree with hereditary trichilemmal cysts

Zhao

Zhou

et al. 2019

Molec Gen & Gen Med

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Background Trichilemmal cysts (TCs) are common intradermal or subcutaneous cysts, which are commonly sporadic and rarely autosomal dominantly inherited. However, little is known about the disease‐determining genes in families with TCs exhibiting Mendelian inheritance. Objective The aim of this study was to identify the causative gene in a family with TCs. Methods Whole‐exome sequencing was performed on a TCs family to identify the candidate gene. Sanger sequencing was conducted to validate the candidate variants and familial segregation. Results We identified the heterozygous variant c.3G>C (p.Met1?) within the BPIFC gene. Sanger sequencing confirmed the cosegregation of this variant with the TCs phenotype in the family by demonstrating the presence of the heterozygous variant in all the 12 affected and absence in all the seven unaffected individuals. This variant was found to be absent in dbSNP141, 1,000 Genomes database and 500 ethnicity matched controls. Conclusion Our results imply that BPIFC is a causative gene in this Chinese family with hereditary TCs. Further studies should be performed to validate the role of BPIFC in the pathogenesis of this disease.

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Plasma lipid transfer proteins: The role of PLTP and CETP in atherogenesis

Cited by 33 publications

References 45 publications

A transcriptome-wide association study based on 27 tissues identifies 106 genes potentially relevant for disease pathology in age-related macular degeneration

A transcriptome-wide association study based on 27 tissues identifies 106 genes potentially relevant for disease pathology in age-related macular degeneration

Modified lipoproteins in periodontitis: a link to cardiovascular disease?

Novel heterozygous BPIFC variant in a Chinese pedigree with hereditary trichilemmal cysts

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