Did you mean: hypolipoproteinemias
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Experimental and Molecular Pathology Apr 2024Interleukin-6 (IL-6) is an acute-phase protein that plays an important role in the inflammatory response, vascular inflammation, and atherosclerosis process. The study...
BACKGROUND AND AIMS
Interleukin-6 (IL-6) is an acute-phase protein that plays an important role in the inflammatory response, vascular inflammation, and atherosclerosis process. The study aimed to establish whether IL-6 gene polymorphisms and IL-6 concentrations are associated with premature coronary artery disease (pCAD) and cardiovascular risk factors.
METHODS
The IL-6 concentrations and the rs2069827, rs1800796, and rs1800795 IL-6 polymorphisms were determined in 1150 pCAD patients and 1083 healthy controls (coronary artery calcium equal to zero determined by tomography).
RESULTS
The IL-6 polymorphisms studied were not associated with pCAD, but they were associated with cardiovascular risk factors in patients and controls. In controls, under the dominant model, the rs1800795 C allele and the rs2069827 T allele were associated with a low risk of central obesity (OR = 0.401, p = 0.017 and OR = 0.577, p = 0.031, respectively), hypoalphalipoproteinemia (OR = 0.581, p = 0.027 and OR = 0.700, p = 0.014, respectively) and hypertriglyceridemia (OR = 0.575, p = 0.030 and OR = 0.728, p = 0.033, respectively). In pCAD, the rs1800795 C allele was associated with an increased risk of hypoalphalipoproteinemia (OR = 1.370, p = 0.025) and increased C-reactive protein (CRP) concentrations (OR = 1.491, p = 0.007). pCAD patients had significantly higher serum IL-6 concentrations compared to controls (p = 0.002). In the total population, individuals carrying the rs1800795 GC + CC genotypes had higher levels of IL-6 than carriers of the GG genotype (p = 0.025). In control individuals carrying the C allele (CG + CC), an inverse correlation was observed between IL-6 and HDL-cholesterol levels (p = 0.003).
CONCLUSIONS
In summary, the IL-6 polymorphisms were not associated with pCAD, however, they were associated with cardiovascular risk factors in pCAD patients and healthy controls. Individuals carrying the rs1800795 GC + CC genotypes had higher levels of IL-6 than carriers of the GG genotype.
Topics: Humans; Cardiovascular Diseases; Case-Control Studies; Coronary Artery Disease; Genetic Predisposition to Disease; Heart Disease Risk Factors; Hypoalphalipoproteinemias; Interleukin-6; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 38290570
DOI: 10.1016/j.yexmp.2024.104886 -
Biomolecules & Biomedicine Mar 2024Interleukin 6 (IL-6) is a cytokine implicated in the development of atherosclerosis. This study aimed to determine the association of three IL-6 gene polymorphisms with...
Increased carotid intima-media thickness and cardiometabolic risk factors are associated with IL-6 gene polymorphisms in Mexican individuals: The Genetics of Atherosclerotic Disease Mexican study.
Interleukin 6 (IL-6) is a cytokine implicated in the development of atherosclerosis. This study aimed to determine the association of three IL-6 gene polymorphisms with increased carotid intima-media thickness (CIMT) and cardiometabolic risk factors. Three IL-6 polymorphisms (rs1800795, rs2069827, and rs1800796) were analyzed in 178 individuals with increased CIMT (CIMT ≥ 75th percentile) and 906 individuals without increased CIMT (CIMT < 75th percentile). Logistic regression, adjusted for confounding variables, was employed to assess the associations. The rs1800796 polymorphism was significantly associated with an elevated risk of increased CIMT (OR = 1.354, Padditive = 0.016; OR = 1.803, Precessive = 0.014; OR = 1.989, Pcodominant2 = 0.008). One haplotype (GCG) correlated with a higher risk of increased CIMT (OR = 1.288; P = 0.008), while another (GGG) demonstrated a reduced risk (OR = 0.773; P = 0.006). In individuals without increased CIMT, the rs2069827 polymorphism was associated with low risks of central obesity, hypoalphalipoproteinemia, and a low risk of presenting with high levels of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C) /HDL-C index, apolipoprotein B, and gamma-glutamyl transpeptidase. The rs1800796 polymorphism was associated with a low risk of adipose tissue insulin resistance, and the rs1800795 was associated with a minimal risk of central obesity and hypoalphalipoproteinemia. Among those with increased CIMT, the rs2069827 was associated with low risks of central obesity, hypertriglyceridemia, metabolic syndrome, and a high triglyceride (TG)/HDL-C index, while rs1800796 was associated with a low risk of fatty liver. Similar IL-6 concentrations were observed in both individuals with and without increased CIMT. In conclusion, the rs1800796 polymorphism is associated with increased CIMT, while the rs2069827 and rs1800795 are linked to cardiovascular risk factors.
Topics: Humans; Atherosclerosis; Cardiometabolic Risk Factors; Carotid Intima-Media Thickness; Cholesterol; Hypoalphalipoproteinemias; Interleukin-6; Obesity; Obesity, Abdominal; Polymorphism, Genetic; Risk Factors
PubMed: 37838929
DOI: 10.17305/bb.2023.9495 -
Journal of Clinical Lipidology 2023Molecular genetic testing of patients with hypobetalipoproteinemia may identify a genetic cause that can form the basis for starting proper therapy. Identifying a...
Missense mutation Q384K in the APOB gene affecting the large lipid transfer module of apoB reduces the secretion of apoB-100 in the liver without reducing the secretion of apoB-48 in the intestine.
BACKGROUND
Molecular genetic testing of patients with hypobetalipoproteinemia may identify a genetic cause that can form the basis for starting proper therapy. Identifying a genetic cause may also provide novel data on the structure-function relationship of the mutant protein.
OBJECTIVE
To identify a genetic cause of hypobetalipoproteinemia in a patient with levels of low density lipoprotein cholesterol at the detection limit of 0.1 mmol/l.
METHODS
DNA sequencing of the translated exons with flanking intron sequences of the genes adenosine triphosphate-binding cassette transporter 1, angiopoietin-like protein 3, apolipoprotein B, apolipoprotein A1, lecithin-cholesterol acyltransferase, microsomal triglyceride transfer protein and proprotein convertase subtilisin/kexin type 9.
RESULTS
The patient was homozygous for mutation Q384K (c.1150C>A) in the apolipoprotein B gene, and this mutation segregated with hypobetalipoproteinemia in the family. Residue Gln is located in the large lipid transfer module of apoB that has been suggested to be important for lipidation of apolipoprotein B through interaction with microsomal triglyceride transfer protein. Based on measurements of serum levels of triglycerides and apolipoprotein B-48 after an oral fat load, we conclude that the patient was able to synthesize apolipoprotein B-48 in the intestine in a seemingly normal fashion.
CONCLUSION
Our data indicate that mutation Q384K severely reduces the secretion of apolipoprotein B-100 in the liver without reducing the secretion of apolipoprotein B-48 in the intestine. Possible mechanisms for the different effects of this and other missense mutations affecting the large lipid transfer module on the two forms of apoB are discussed.
Topics: Humans; Apolipoprotein B-100; Apolipoprotein B-48; Mutation, Missense; Apolipoproteins B; Intestines; Hypobetalipoproteinemias; Mutation; Liver
PubMed: 37718180
DOI: 10.1016/j.jacl.2023.08.009 -
Clinica E Investigacion En... 2023Primary hypocholesterolemia (or hypobetalipoproteinemia) is a rare disorder of lipoprotein metabolism that may be due to a polygenic predisposition or a monogenic...
Primary hypocholesterolemia (or hypobetalipoproteinemia) is a rare disorder of lipoprotein metabolism that may be due to a polygenic predisposition or a monogenic disease. Among these, it is possible to differentiate between symptomatic and asymptomatic forms, in which, in the absence of secondary causes, the initial clinical suspicion is plasma ApoB levels below the 5th percentile of the distribution by age and sex. Here we describe the differential diagnosis of a case of asymptomatic hypocholesterolemia. We studied proband's clinical data, the lipid profile of the proband and her relatives and the clinical data of the family relevant to carry out the differential diagnosis. We performed a genetic study as the diagnostic test. The information obtained from the differential diagnosis suggested a heterozygous hypobetalipoproteinemia due to PCSK9 loss-of-function variants. The diagnostic test revealed, in the proband, the presence of a heterozygous PCSK9 frame-shift variant of a maternal origin. Plasma levels of LDL cholesterol and PCSK9 of the patient and her relatives were compatible with the segregation of the variant revealed. In conclusion, the diagnostic test performed confirmed the suspected diagnosis of the proband as asymptomatic familial hypobetalipoproteinemia due to a loss-of-function variant in the PCSK9 gene.
Topics: Humans; Female; Proprotein Convertase 9; Hypobetalipoproteinemias; Hypolipoproteinemias; Cholesterol, LDL; Apolipoproteins B
PubMed: 37302939
DOI: 10.1016/j.arteri.2023.05.003 -
PloS One 2023Dyslipidemias are defined as a wide range of abnormalities of the lipid profile. Treatment guidelines recommend aiming at lowering LDL-C. We investigated the adherence...
Dyslipidemias are defined as a wide range of abnormalities of the lipid profile. Treatment guidelines recommend aiming at lowering LDL-C. We investigated the adherence of Czech cardiologists to the dyslipidaemia treatment guidelines, especially in the management of patients with high and very high cardiovascular risk. In this retrospective cross-sectional multicentric study data from medical records of 450 adults with ASCVD, enrolled between June 2021 and January 2022, were analysed. Demographics, clinical outcomes, medical history, LLT treatment and other medications were collected. The physicians were to include patients at a very high risk of ASCVD and to complete a general questionnaire on their personal therapeutic preferences. Objectively assessed, only 80% of total patients (N = 450) enrolled in the study were at very high risk of ASCVD, and 12.7% of patients were at high risk of ASCVD, respectively. In total, 55 (13.1%) patients were diagnosed with familial hypercholesterolemia, and 39.1% of them had a positive family history of ASCVD. Generally, only 20.5% of patients reached the 2019 LDL-C goals- 19.4% of very high risk patients and 28.1% of high risk patients, respectively. 61% of the physicians preferred a slow and careful up-titration of the dose, which is contradictory to the guidelines. Only 17% of the physicians increased the statin dose or added/combined/changed the treatment to achieve the LDL-C goals as soon as possible. Surprisingly, in up to 61.5% of patients at very high risk who did not meet the LDL-C goals, their physicians stated subjective satisfaction with the treatment and considered no change needed. Among very high and high risk patients receiving lipid-lowering therapy, with high treatment adherence, the LDL-C goal attainment is very low and LLT utilization is rather sub-optimal. Improving observance of the guidelines by physicians bears a substantial potential for LDL-C goal attainment and thus improving overall benefit for patients for no additional costs.
Topics: Adult; Humans; Cholesterol, LDL; Cardiovascular Diseases; Retrospective Studies; Cross-Sectional Studies; Goals; Risk Factors; Treatment Outcome; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Dyslipidemias; Hypolipoproteinemias; Heart Disease Risk Factors
PubMed: 37216363
DOI: 10.1371/journal.pone.0272883 -
Kardiologia Polska 2023
Topics: Humans; Tangier Disease; Gold; Atherosclerosis; Patients
PubMed: 36871306
DOI: 10.33963/KP.a2023.0061 -
Journal of Ayub Medical College,... 2023Klipple-Trenaunay syndrome (KTS) is an extremely rare congenital vascular disorder with poorly defined incidence and prevalence. We report a case of a patient who...
Klipple-Trenaunay syndrome (KTS) is an extremely rare congenital vascular disorder with poorly defined incidence and prevalence. We report a case of a patient who presented after road traffic accident with primary complaints of poor wound healing and persistent bleeding from wound site. Discernible presence of arteriovenous malformation and skin hypertrophy since birth lead to the diagnosis of Klipple-Trenaunay syndrome (KTS). There was an incidental finding of acanthocytosis on peripheral film of blood which remained elevated even after clinical improvement of the patient. This case report highlights a close association of marked acanthocytosis of red blood cells and Klipple-Trenaunay syndrome.
Topics: Humans; Abetalipoproteinemia; Erythrocytes
PubMed: 36849406
DOI: 10.55519/JAMC-01-11307 -
Nutrients Jan 2023Abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3) are rare recessive disorders of lipoprotein metabolism due to mutations in and genes,...
Abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3) are rare recessive disorders of lipoprotein metabolism due to mutations in and genes, respectively, which lead to defective chylomicron formation and secretion. This results in lipid and fat-soluble vitamin malabsorption, which induces severe neuro-ophthalmic complications. Currently, treatment combines a low-fat diet with high-dose vitamin A and E supplementation but still fails in normalizing serum vitamin E levels and providing complete ophthalmic protection. To explore these persistent complications, we developed two knock-out cell models of FHBL-SD1 and FHBL-SD3 using the CRISPR/Cas9 technique in Caco-2/TC7 cells. DNA sequencing, RNA quantification and Western blotting confirmed the introduction of mutations with protein knock-out in four clones associated with i) impaired lipid droplet formation and ii) defective triglyceride (-57.0 ± 2.6% to -83.9 ± 1.6%) and cholesterol (-35.3 ± 4.4% to -60.6 ± 3.5%) secretion. A significant decrease in α-tocopherol secretion was also observed in these clones (-41.5 ± 3.7% to -97.2 ± 2.8%), even with the pharmaceutical forms of vitamin E: tocopherol-acetate and tocofersolan (α-tocopheryl polyethylene glycol succinate 1000). silencing led to a more severe phenotype than silencing, which is consistent with clinical observations. Our cellular models thus provide an efficient tool to experiment with therapeutic strategies and will allow progress in understanding the mechanisms involved in lipid metabolism.
Topics: Humans; alpha-Tocopherol; Apolipoproteins B; Caco-2 Cells; Enterocytes; Hypobetalipoproteinemias; Monomeric GTP-Binding Proteins; Vitamin E
PubMed: 36771214
DOI: 10.3390/nu15030505 -
CEN Case Reports Aug 2023Rarely, disorders of lipid metabolism cause nephrotic syndrome with progressive kidney disease. Tangier disease is a rare condition belonging to this family of lipid...
Rarely, disorders of lipid metabolism cause nephrotic syndrome with progressive kidney disease. Tangier disease is a rare condition belonging to this family of lipid disorders; however, it is not associated with kidney disease. We report a patient presenting with nephrotic syndrome, leading to the unmasking of Tangier disease. A 34-year-old man presented with ankle oedema, nephrotic-range proteinuria and hypoalbuminaemia. Kidney biopsy demonstrated membranous nephropathy with features of immunoperoxidase staining, suggesting a secondary aetiology. Acute serology was negative. Imaging showed lymphadenopathy with splenomegaly suggestive of lymphoproliferative disorder. Bone marrow biopsy revealed foamy macrophages with widespread lipid deposition. Genomic sequencing revealed a pathological homozygous variant for ATP-binding cassette subfamily A member 1 (ABCA1) c.1510-1G > A, consistent with Tangier disease. Review of the ultrastructural kidney biopsy features demonstrated, in addition to membranous subepithelial and intramembranous usual-type electron-dense deposits, intramembranous osmiophilic lipid deposits similar to those in LCAT deficiency. The patient's renal function gradually declined (serum creatinine 133 µmol/L); therefore, he was started on rituximab. Metabolic disorders causing nephrotic syndrome are rare and even more so their association with membranous nephropathy. These should be considered in cases with unexplained persistent nephrotic syndrome with progressive kidney disease and lipid deposits on renal biopsy.
Topics: Male; Humans; Adult; Nephrotic Syndrome; Glomerulonephritis, Membranous; Tangier Disease; Kidney; Lipids
PubMed: 36496495
DOI: 10.1007/s13730-022-00761-8 -
Metabolomics : Official Journal of the... Dec 2022Previous study has shown that dyslipidemia is common in patients with Sickle cell disease (SCD) and is associated with more serious SCD complications.
BACKGROUND
Previous study has shown that dyslipidemia is common in patients with Sickle cell disease (SCD) and is associated with more serious SCD complications.
METHODS
This study investigated systematically dyslipidemia in SCD using a state-of-art nuclear magnetic resonance (NMR) metabolomics platform, including 147 pediatric cases with SCD and 1234 controls without SCD. We examined 249 metabolomic biomarkers, including 98 biomarkers for lipoprotein subclasses, 70 biomarkers for relative lipoprotein lipid concentrations, plus biomarkers for fatty acids and phospholipids.
RESULTS
Specific patterns of hypolipoproteinemia and hypocholesterolemia in pediatric SCD were observed in lipoprotein subclasses other than larger VLDL subclasses. Triglycerides are not significantly changed in SCD, except increased relative concentrations in lipoprotein subclasses. Decreased plasma FFAs (including total-FA, SFA, PUFA, Omega-6, and linoleic acid) and decreased plasma phospholipids were observed in SCD.
CONCLUSION
This study scrutinized, for the first time, lipoprotein subclasses in pediatric patients with SCD, and identified SCD-specific dyslipidemia from altered lipoprotein metabolism. The findings of this study depict a broad panorama of lipid metabolism and nutrition in SCD, suggesting the potential of specific dietary supplementation of the deficient nutrients for the management of SCD.
Topics: Humans; Child; Metabolomics; Dyslipidemias; Anemia, Sickle Cell; Plasma; Triglycerides
PubMed: 36459297
DOI: 10.1007/s11306-022-01954-z