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Genetic Testing and Molecular Biomarkers Sep 2023Apolipoprotein A5 (APOA5) is involved in serum triglyceride (TG) regulation. Several studies have reported that the rs651821 locus in the gene is associated with serum...
Apolipoprotein A5 (APOA5) is involved in serum triglyceride (TG) regulation. Several studies have reported that the rs651821 locus in the gene is associated with serum TG levels in the Chinese population. However, no research has been performed regarding the association between the variants of rs651821 and the risk of hyperlipidemic acute pancreatitis (HLAP). A case-control study was conducted and is reported following the STROBE guidelines. We enrolled a total of 88 participants in this study (60 HLAP patients and 28 controls). was genotyped using PCR and Sanger sequencing. Logistic regression models were conducted to calculate odds ratios and a 95% confidence interval. The genotype distribution of the rs651821 alleles in both groups follow the Hardy-Weinberg distribution. The frequency of the "C" allele in rs651821 was increased in HLAP patients compared to controls. In the recessive model, subjects with the "CC" genotype had an 8.217-fold higher risk for HLAP (OR = 8.217, 95% CI: 1.023-66.01, = 0.046) than subjects with the "TC+TT" genotypes. After adjusting for sex, the association remained significant (OR = 9.898, 95% CI: 1.176-83.344, = 0.035). Additionally, the "CC" genotype was related to an increased TG/apolipoprotein B (APOB) ratio and fasting plasma glucose (FPG) levels. Our findings suggest that the C allele of rs651821 in increases the risk of HLAP in persons from Southeastern China.
Topics: Humans; Apolipoprotein A-V; Apolipoproteins A; Genetic Predisposition to Disease; Case-Control Studies; Acute Disease; Polymorphism, Single Nucleotide; Pancreatitis; Genotype; China; Gene Frequency; Triglycerides
PubMed: 37768328
DOI: 10.1089/gtmb.2023.0107 -
Journal of Cellular and Molecular... Jun 2024Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly...
Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD-free individuals were enrolled in this case-control study. The rs1801133 variant was genotyped by PCR-RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD-free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs-CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions.
Topics: Humans; Homocysteine; Male; Coronary Artery Disease; Middle Aged; Female; Case-Control Studies; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Single Nucleotide; Severity of Illness Index; Aged; Risk Factors; Genetic Predisposition to Disease; ROC Curve; Genotype; C-Reactive Protein; Alleles; Apolipoprotein A-I
PubMed: 38896027
DOI: 10.1111/jcmm.18474 -
Scientific Reports May 2024Dyslipidaemias is the leading risk factor of several major cardiovascular diseases (CVDs), but there is still a lack of sufficient evidence supporting a causal role of... (Observational Study)
Observational Study
Dyslipidaemias is the leading risk factor of several major cardiovascular diseases (CVDs), but there is still a lack of sufficient evidence supporting a causal role of lipoprotein subspecies in CVDs. In this study, we comprehensively investigated several lipoproteins and their subspecies, as well as other metabolites, in relation to coronary heart disease (CHD), heart failure (HF) and ischemic stroke (IS) longitudinally and by Mendelian randomization (MR) leveraging NMR-measured metabolomic data from 118,012 UK Biobank participants. We found that 123, 110 and 36 analytes were longitudinally associated with myocardial infarction, HF and IS (FDR < 0.05), respectively, and 25 of those were associated with all three outcomes. MR analysis suggested that genetically predicted levels of 70, 58 and 7 analytes were associated with CHD, HF and IS (FDR < 0.05), respectively. Two analytes, ApoB/ApoA1 and M-HDL-C were associated with all three CVD outcomes in the MR analyses, and the results for M-HDL-C were concordant in both observational and MR analyses. Our results implied that the apoB/apoA1 ratio and cholesterol in medium size HDL were particularly of importance to understand the shared pathophysiology of CHD, HF and IS and thus should be further investigated for the prevention of all three CVDs.
Topics: Humans; Mendelian Randomization Analysis; Cardiovascular Diseases; Male; Female; Risk Factors; Middle Aged; Magnetic Resonance Spectroscopy; Apolipoprotein A-I; Aged; Cholesterol, HDL; Coronary Disease; Metabolomics; Apolipoprotein B-100; Ischemic Stroke; Heart Failure
PubMed: 38724583
DOI: 10.1038/s41598-024-61440-5 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Sep 2023To investigate the apolipoprotein C-3 (APOC3) gene Ⅰ polymorphism and its relationship with changes in serum lipids in patients with gestational diabetes mellitus (GDM).
OBJECTIVE
To investigate the apolipoprotein C-3 (APOC3) gene Ⅰ polymorphism and its relationship with changes in serum lipids in patients with gestational diabetes mellitus (GDM).
METHODS
A total of 630 pregnant women with GDM and 1027 normal pregnant controls were covered in the study. The genotype and allele frequencies of 3 Ⅰ polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose (Glu) were measured by enzymatic methods. Plasma insulin (INS) was measured by chemiluminescence. Apolipoproteins A 1 (apoA1) and B (apoB) levels were measured by turbidimetric immunoassay.
RESULTS
The allele frequencies of S1 and S2 of the 3 polymorphism at the Ⅰ locus were 0.704 and 0.296 in the GDM group and 0.721 and 0.279 in the control group, respectively. There was no significant difference in genotype frequency and allele frequency of 3 Ⅰ polymorphism between the GDM and the control groups ( >0.05). In the GDM group, those with S2S2 and S1S2 genotypes had higher plasma HDL-C levels and lower atherogenic index (AI) values than those with S1S1 genotype did, with the differences being statistically significant (all <0.05). GDM patients were then divided into obesity and non-obesity subgroups. Further subgroup analysis showed that the association of 3 genotype with changes in HDL-C levels was observed only in obese GDM patients, while the association of 3 genotype with changes in AI values was observed in both obese and nonobese patients. In addition, in obese GDM patients, those with S2S2 genotype had significantly higher plasma TG levels than those with S1S1 and S1S2 genotypes did ( <0.05 and <0.01, respectively). In non-obese GDM patients, those with S2S2 genotype had significantly lower apoB/apoA1 ratio than S2S2 carriers did ( <0.05). No genotype-related effect on lipid and apolipoprotein variations was evident in the normal controls.
CONCLUSION
3 Ⅰ polymorphism in GDM patients is associated with HDL-C and TG levels as well as AI value and apoB/apoA1 ratio. The changes in lipid levels and apolipoprotein ratio showed BMI-dependent features. However, association between polymorphism at the locus and the development of GDM was not observed.
Topics: Female; Humans; Pregnancy; Apolipoprotein A-I; Apolipoprotein C-III; Apolipoproteins B; Apolipoproteins C; Cholesterol, HDL; Diabetes, Gestational; Gene Frequency; Genotype; Obesity; Triglycerides
PubMed: 37866958
DOI: 10.12182/20230960505 -
Biochimica Et Biophysica Acta.... Dec 2023Surface lipids influence the biological activities of high-density lipoproteins (HDLs) but their species-specific effects on HDL structure, dynamics, and surface...
Surface lipids influence the biological activities of high-density lipoproteins (HDLs) but their species-specific effects on HDL structure, dynamics, and surface interactome has remained unclear. Building upon the five-lipid species HDL models developed and characterised in previous work, representative models of the major HDL subpopulations found in human plasma containing apolipoprotein A-I (apoA-I) have been studied using molecular dynamics simulation to describe their varying degrees of surface lipidome complexity. Specifically, two additional sets of representative HDL subpopulation particles were developed, one with sphingomyelin (SM) and the other with SM, phosphatidylethanolamine, phosphatidylinositol, and ceramide in quantities reflecting average levels characterised for HDL subpopulations derived from normolipidemic patients. These lipid species were assessed in terms of HDL size, morphology, dynamics, and overall interactome. The findings reveal that the presence of a representative SM fraction marginally enhanced HDL interfacial curvature and surface monolayer rigidity, manifesting in tighter phospholipid packing and slower surface lipid dynamics relative to SM-deficient HDL models. Furthermore, the presence of SM resulted in a reduction in the solvent exposure of core lipids and cholesterol molecules, whilst also enhancing apolipoprotein conformational flexibility and its overall twisting across the HDL surface. The hydrophobicity of apoA-I-bound lipid patches and the proportion of apoA-I hydrophobic surface area is enhanced by the overall lipidation of apoA-I irrespective of lipid composition. These findings offer new insights into how the surface lipid composition of different HDL subpopulations can significantly impact the overall interactome of HDL particles, potentially influencing subpopulation-specific biological functions like lipid scavenging and receptor interactions.
Topics: Humans; Apolipoprotein A-I; Lipoproteins, HDL; Cholesterol; Phospholipids; Apolipoproteins
PubMed: 37541644
DOI: 10.1016/j.bbamem.2023.184201 -
Journal of Orthopaedic Surgery and... Apr 2024To analyze the relationship between lipid metabolism, coagulation function, and bone metabolism and the contributing factor and staging of non-traumatic femoral head...
Relationship between lipid metabolism, coagulation and other blood indices and etiology and staging of non-traumatic femoral head necrosis: a multivariate logistic regression-based analysis.
BACKGROUND
To analyze the relationship between lipid metabolism, coagulation function, and bone metabolism and the contributing factor and staging of non-traumatic femoral head necrosis, and to further investigate the factors influencing the blood indicators related to the staging of non-traumatic femoral head necrosis.
METHODS
The medical records of patients with femoral head necrosis were retrieved from the inpatient medical record management system, and the lipid metabolism, bone metabolism, and coagulation indices of non-traumatic femoral head necrosis (including alcoholic, hormonal, and idiopathic group) were obtained according to the inclusion and exclusion criteria, including Low-Density Lipoprotein Cholesterol, Triglycerides, Non-High-Density Lipoprotein Cholesterol, Apolipoprotein A1, Apolipoprotein (B), Apolipoprotein (E), Uric Acid, Alkaline Phosphatase, Bone-specific Alkaline Phosphatase, Activated Partial Thromboplastin Time, Prothrombin Time, D-dimer, Platelet count. The relationship between these blood indices and the different stages under different causative factors was compared, and the factors influencing the stages of non-traumatic femoral head necrosis were analyzed using multivariate logistic regression.
RESULTS
(i) Gender, Age and BMI stratification, Low-density Lipoprotein Cholesterol, Triglycerides, Non-High-density Lipoprotein Cholesterol, Apolipoprotein (B), Apolipoprotein (E), Uric Acid, Bone-specific Alkaline Phosphatase, Activated Partial Thromboplastin Time, Plasminogen Time, D-dimer, and Platelet count of the alcohol group were statistically different when compared among the different ARCO staging groups; (ii) The differences in Age and BMI stratification, Triglycerides, Non-High-density Lipoprotein Cholesterol, Apolipoprotein A1, Apolipoprotein B, Apolipoprotein E, Uric Acid, Bone-specific Alkaline Phosphatase, Activated Partial Thromboplastin Time, Plasminogen Time, D-dimer, and Platelet count were statistically significant when compared among the different phases in the hormone group (P < 0.05); (iii) The differences in Age and BMI stratification, Non-High-Density Lipoprotein Cholesterol, Apolipoprotein A1, Apolipoprotein (B), Apolipoprotein (E), Uric Acid, Activated Partial Thromboplastin Time, D-dimer, and Platelet count were statistically significant when compared among the different stages in the idiopathic group (P < 0.05); (v) Statistically significant indicators were included in the multivariate logistic regression analysis, excluding the highly correlated bone-specific alkaline phosphatase, and the results showed that Low-density lipoprotein was negatively correlated with changes in the course of ARCO, and Non-High-Density Lipoprotein cholesterol, Apo B, Activated Partial Thromboplastin Time, and Platelet count were significantly and positively correlated with disease progression.
CONCLUSION
An abnormal hypercoagulable state as well as an abnormal hyperlipidemic state are risk factors for the progression of non-traumatic femoral head necrosis under various exposure factors, as indicated by Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, Activated Fractional Thromboplastin Time, and Platelet Counts.
Topics: Humans; Apolipoprotein A-I; Logistic Models; Lipid Metabolism; Femur Head Necrosis; Alkaline Phosphatase; Uric Acid; Cholesterol; Triglycerides; Cholesterol, LDL; Plasminogen
PubMed: 38643101
DOI: 10.1186/s13018-024-04715-x -
Nutrients Nov 2023Obesity is one of the main risk factors for cardiovascular diseases, type II diabetes, hypertension, and certain cancers. Obesity in women at the reproductive stage...
Obesity is one of the main risk factors for cardiovascular diseases, type II diabetes, hypertension, and certain cancers. Obesity in women at the reproductive stage adversely affects contraception, fertility, maternal well-being, and the health of their offspring. Being a major protein component in chylomicrons and high-density lipoproteins, apolipoprotein A-IV (apoA-IV) is involved in lipid metabolism, food intake, glucose homeostasis, prevention against atherosclerosis, and platelet aggregation. The goal of the present study is to determine the impact of apoA-IV deficiency on metabolic functions in 129X1/SvJ female mouse strain. After chronic high-fat diet feeding, apoA-IV mice gained more weight with a higher fat percentage than wild-type (WT) mice, as determined by measuring their body composition. Increased adiposity and adipose cell size were also observed with a microscope, particularly in periovarian fat pads. Based on plasma lipid and adipokine assays, we found that obesity in apoA-IV mice was not associated with hyperlipidemia but with higher leptin levels. Compared to WT mice, apoA-IV deficiency displayed glucose intolerance and elevated insulin levels, according to the data of the glucose tolerance test, and increased HOMA-IR values at fasting, suggesting possible insulin resistance. Lastly, we found obesity in apoA-IV mice resulting from reduced energy expenditure but not food intake. Together, we established a novel and excellent female mouse model for future mechanistic study of obesity and its associated comorbidities.
Topics: Female; Humans; Mice; Animals; Insulin Resistance; Diabetes Mellitus, Type 2; Apolipoproteins A; Obesity; Mice, Inbred Strains; Diet, High-Fat; Energy Metabolism; Mice, Inbred C57BL
PubMed: 37960308
DOI: 10.3390/nu15214655 -
Arteriosclerosis, Thrombosis, and... Feb 2024High cholesterol levels in pancreatic β-cells cause oxidative stress and decrease insulin secretion. β-cells can internalize apo (apolipoprotein) A-I, which increases...
BACKGROUND
High cholesterol levels in pancreatic β-cells cause oxidative stress and decrease insulin secretion. β-cells can internalize apo (apolipoprotein) A-I, which increases insulin secretion. This study asks whether internalization of apoA-I improves β-cell insulin secretion by reducing oxidative stress.
METHODS
Ins-1E cells were cholesterol-loaded by incubation with cholesterol-methyl-β-cyclodextrin. Insulin secretion in the presence of 2.8 or 25 mmol/L glucose was quantified by radioimmunoassay. Internalization of fluorescently labeled apoA-I by β-cells was monitored by flow cytometry. The effects of apoA-I internalization on β-cell gene expression were evaluated by RNA sequencing. ApoA-I-binding partners on the β-cell surface were identified by mass spectrometry. Mitochondrial oxidative stress was quantified in β-cells and isolated islets with MitoSOX and confocal microscopy.
RESULTS
An F-ATPase β-subunit on the β-cell surface was identified as the main apoA-I-binding partner. β-cell internalization of apoA-I was time-, concentration-, temperature-, cholesterol-, and F-ATPase β-subunit-dependent. β-cells with internalized apoA-I (apoA-I cells) had higher cholesterol and cell surface F-ATPase β-subunit levels than β-cells without internalized apoA-I (apoA-I cells). The internalized apoA-I colocalized with mitochondria and was associated with reduced oxidative stress and increased insulin secretion. The IF (ATPase inhibitory factor 1) attenuated apoA-I internalization and increased oxidative stress in Ins-1E β-cells and isolated mouse islets. Differentially expressed genes in apoA-I and apoA-I Ins-1E cells were related to protein synthesis, the unfolded protein response, insulin secretion, and mitochondrial function.
CONCLUSIONS
These results establish that β-cells are functionally heterogeneous, and apoA-I restores insulin secretion in β-cells with elevated cholesterol levels by improving mitochondrial redox balance.
Topics: Mice; Animals; Insulin; Apolipoprotein A-I; Insulin-Secreting Cells; Cholesterol; Glucose; Adenosine Triphosphatases
PubMed: 38095105
DOI: 10.1161/ATVBAHA.123.319378 -
International Heart Journal Jul 2023This study aims to assess the predictive value of the apolipoprotein B (ApoB) /apolipoprotein A1 (ApoA1) ratio in acute coronary syndrome (ACS) in patients with diabetes...
The Value of the Apolipoprotein B/Apolipoprotein A1 Ratio in Predicting the Rapid Progression of Non-Culprit Coronary Lesions in Acute Coronary Syndrome in Patients with Diabetes Mellitus after Percutaneous Coronary Intervention.
This study aims to assess the predictive value of the apolipoprotein B (ApoB) /apolipoprotein A1 (ApoA1) ratio in acute coronary syndrome (ACS) in patients with diabetes mellitus (DM) for the rapid progression (RP) of non-culprit coronary lesions (NCCLs) after percutaneous coronary intervention (PCI) and observe the effect of the ApoB/ApoA1 ratio on major adverse cardiac events (MACE).A total of 175 patients with DM presenting with ACS who received a PCI and an average 13-month follow-up coronary angiography (CAG) were enrolled from January 2015 to December 2020. According to the CAG, the patients were divided into the RP group and the non-RP group. MACE was defined as a composite of death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization from unstable or progressive angina at the end of a 24-month follow-up.The low-density lipoprotein cholesterol (LDL-C), ApoB, ApoB/ApoA1 ratio, and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio levels at baseline were significantly higher in the RP group than in the non-RP group. The ApoA1 level at baseline in the non-RP group was significantly higher than in the RP group. The predictive significance of the ApoB/ApoA1 ratio (area under the curve (AUC) = 0.712) for the RP of NCCLs was significantly higher than those of ApoA1, ApoB, LDL-C/HDL-C ratio (AUC = 0.628, AUC = 0.640, and AUC = 0.620, respectively). A higher ApoB/ApoA1 ratio and the RP of NCCLs were significantly associated with the occurrence of MACE.The ApoB/ApoA1 ratio was an effective clinical indicator for the RP of NCCLs after PCI in patients with DM presenting with ACS. The high ApoB/ApoA1 ratio and the RP of NCCLs were two risks for MACE.
Topics: Humans; Acute Coronary Syndrome; Cholesterol, LDL; Apolipoprotein A-I; Percutaneous Coronary Intervention; Apolipoproteins B; Diabetes Mellitus
PubMed: 37460319
DOI: 10.1536/ihj.22-676 -
Nutrients Nov 2023Apolipoprotein A-IV (apoA-IV), synthesized by enterocytes, is potentially involved in regulating lipid absorption and metabolism, food intake, and glucose metabolism. In...
Apolipoprotein A-IV (apoA-IV), synthesized by enterocytes, is potentially involved in regulating lipid absorption and metabolism, food intake, and glucose metabolism. In this study, we backcrossed apoA-IV knockout (apoA-IV) mice onto the 129/SvJ background for eight generations. Compared to the wild-type (WT) mice, the 129/SvJ apoA-IV mice gained more weight and exhibited delayed glucose clearance even on the chow diet. During a 16-week high-fat diet (20% by weight of fat) study, apoA-IV mice were more obese than the WT mice, which was associated with their increased food intake as well as reduced energy expenditure and physical activity. In addition, apoA-IV mice developed significant insulin resistance (indicated by HOMA-IR) with severe glucose intolerance even though their insulin levels were drastically higher than the WT mice. In conclusion, we have established a model of apoA-IV mice onto the 129/SvJ background. Unlike in the C57BL/6J strain, apoA-IV 129/SvJ mice become significantly more obese and insulin-resistant than WT mice. Our current investigations of apoA-IV in the 129/SvJ strain and our previous studies in the C57BL/6J strain underline the impact of genetic background on apoA-IV metabolic effects.
Topics: Mice; Animals; Glucose Intolerance; Mice, Inbred C57BL; Apolipoproteins A; Obesity; Diet, High-Fat; Insulin; Mice, Knockout
PubMed: 38004234
DOI: 10.3390/nu15224840