Association Of apoB Research Articles

The Correlation of Apolipoprotein B with Alterations in Specific Fat Depots Content in Adults.

Body mass index (BMI) and blood biomarkers are not enough to predict cardiovascular disease risk. Apolipoprotein B was identified to be associated with cardiovascular disease (CVD) progression. The Dual-energy X-ray Absorption (DXA) results could be considered as a predictor for cardiovascular disease in a more refined way based on fat distribution. The prediction of CVD risk by simple indicators still cannot meet clinical needs. The association of ApoB with specific fat depot features remains to be explored to better co-predict cardiovascular disease risk. An amount of 5997 adults from National Health and Nutrition Examination Survey (NHANES) were enrolled. Their demographic information, baseline clinical condition, blood examination, and DXA physical examination data were collected. Multivariate regression was used to assess the correlation between ApoB and site-specific fat characteristics through different adjusted models. Smooth curve fittings and threshold analysis were used to discover the turning points with 95% confidence intervals. ApoB is positively correlated with arms percent fat, legs percent fat, trunk percent fat, android percent fat, gynoid percent fat, arm circumference and waist circumference after adjustment with covariates for age, gender, race, hypertension, diabetes, hyperlipidemia, coronary heart disease, smoking status and vigorous work activity. The smooth curve fitting and threshold analysis also showed that depot-specific fat had lower turning points of ApoB in both males and females within the normal reference range of ApoB. Meanwhile, females have a lower increase in ApoB per 1% total percent fat and android percent fat than males before the turning points, while females have a higher growth of ApoB per 1% gynoid percent fat than males. The combined specific fat-depot DXA and ApoB analysis could indicate the risk of CVD in advance of lipid biomarkers or DXA alone.

Associations between maternal mid-pregnancy apolipoprotein A-1, apolipoprotein B, apolipoprotein B/apolipoprotein A-1 ratio and preterm birth

Background and aimsElevated lipid levels during pregnancy have been shown to be related to the risk of preterm birth. Despite the importance of apolipoprotein (Apo) in lipid metabolism and transportation, evidence regarding apolipoprotein levels during pregnancy and preterm birth is still limited. Therefore, we aim to investigate the associations between maternal ApoA-1, ApoB, ApoB/ApoA-1 ratio and preterm birth. Materials and methData were extracted from the information system of Guangdong Women and Children Hospital. Lipoprotein levels were tested using Beckman Coulter AU5800 in mid-pregnancy at a median gestational age of 18 w. Maternal serum ApoB, ApoA-1 and ApoB/ApoA-1 ratio were categorized into tertiles. Logistic regression models were performed to evaluate the odds ratios and 95% confidence intervals for preterm birth. ResultsA total of 5,986 maternal-newborn pairs were included in this study. The rate of preterm birth was 5.7% (n = 344). The multivariate-adjusted ORs (95% CI) of preterm birth were 1.51 (1.06, 2.10) for individuals with high ApoB (>90th), 0.63 (0.38, 0.99) for those with low ApoB (<10th), and 1.64 (1.18, 2.24) for those with high ApoB/ApoA-1 (>90th). Subgroup analyses showed that the association of ApoB and preterm birth was only significant among women with pre-pregnancy BMI 18.5-24 kg/m2 (OR = 1.36, 95% CI: 1.12–1.65), age at delivery ≥ 35 years (OR = 1.43, 95% CI: 1.12–1.83). ConclusionElevated maternal ApoB level and ApoB/ApoA-1 ratio during mid-pregnancy were related to increased risk of preterm birth. Monitoring maternal serum apolipoprotein levels may help to identify the high-risk population of preterm birth.

Lipoprotein Levels in Early Adulthood and NAFLD in Midlife: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Objective We evaluated the association of apolipoprotein B (apoB) with low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TG) in early adulthood with concordant/discordant associations and midlife NAFLD. Methods Participants from the CARDIA study were included (n = 2,655; baseline mean age: 25.0, 59.1% female, and 48.6% black). NAFLD was defined as liver attenuation ≤40 Hounsfield units after excluding other causes of liver fat. Logistic regression models assessed the odds of Y25 NAFLD among tertiles of apoB, LDL-C, non-HDL-C, and TG and quartiles of the apoB/TG ratio. Discordance/concordance analyses examined the association of apoB with each lipid marker and Y25 NAFLD. Results The Y25 NAFLD prevalence was 10%. The high-tertile TG group (OR 1.87, 95% CI, and 1.30–2.69) and the low- (OR 1.98, 95% CI, and 1.30–3.01) and middle-apoB/TG ratio groups (OR 1.78, 95% CI, and 1.17–2.72) had the greatest odds of midlife NAFLD. Using discordance/concordance analysis, the high-apoB/high-TG group had the highest odds of NAFLD (OR 1.69, 95% CI, and 1.09–2.61) followed by the low-apoB/high-TG group. The high apoB/low TG group had the lowest odds of NAFLD. Conclusions Among the studied lipid markers in early adulthood, TG levels have the strongest and most consistent association with midlife NAFLD.

Single Nucleotide Polymorphisms in Apolipoprotein B, Apolipoprotein E, and Methylenetetrahydrofolate Reductase Are Associated With Serum Lipid Levels in Northern Chilean Subjects. A Pilot Study.

Characterization of allelic variants is relevant to demonstrate associations among genetic background and susceptibility to develop cardiovascular diseases, which are the main cause of death in Chile. Association of APOB, APOE, and MTHFR polymorphisms with higher lipid levels and the risk of developing hypertension and cardiovascular diseases have been described. Thus, the aim of this study was to assess genotype distribution and relative allelic frequency of ApoB rs693, ApoE rs7412, ApoE rs429358, MTHFR rs1801131, and MTHFR rs1801133 allelic variants and their effects on lipid profile in young healthy men and women from Northern Chile. A group of 193 healthy subjects were enrolled for this study. Genotyping of rs693 (APOB), rs7412 and rs429358 (APOE), and rs1801131 and rs1801133 (MTHFR) polymorphisms were performed by real time PCR. In addition, lipid profiles were determined and associated to genetic data. The genotype distribution was APOB rs693 (CC = 37%, CT = 41%, and TT = 22%), APOE rs7412/rs429358 (E4 = 0.06, E3 = 0.91, and E2 = 0.03), MTHFR rs1801131 (AA = 57%, AC = 30%, and CC = 13%), and MTHFR rs1801133 (CC = 20%, CT = 47%, and TT = 33%). The association of the genetic variants with plasma lipid levels showed that women, but not men, carrying APOB mutated allele (T) and Apo E4 allele presented lower values of total cholesterol when compared with C/C homozygous genotype or E3 allele, respectively (p < 0.05). In addition, a subgroup analysis revealed that ApoB C/C homozygous women exhibited higher values of HDL-C when compared with men carrying identical genotype (p < 0.01). On the other hand, women carrying E4 allele exhibited lower values of triglycerides when compared with male carrying identical genotype (p < 0.05). Finally, women carrying mutate allele (C) for MTHFR rs1801131 showed lower levels of triglycerides when compared with A/A homozygous genotype (p < 0.05) and lower levels of LDL-C for MTHFR rs1801133 in females carrying (T) allele when compared with males carrying identical genotype (p < 0.05). In summary, the present data showed that APOB, APOE, and MTHFR single nucleotide polymorphisms are associated to lipid levels in a gender-dependent manner among healthy subjects from Northern Chile, especially in women.

Association of APOB and LIPC polymorphisms with type 2 diabetes in Chinese Han population

BackgroundApolipoprotein B (APOB), and hepatic lipase (LIPC) genes have been shown to play a key role in lipid metabolism in type 2 diabetes (T2D). This study aimed to investigate the association of the three polymorphisms (rs679899 in APOB and rs6078 and rs6083 in LIPC) with T2D and related clinical quantitative traits. MethodsWe conducted a case-control study in Chinese Han population, with a total of 929 T2D patients and 1044 healthy subjects in Chinese Han population. Polymorphisms were genotyped by MassARRAY Genotyping System. ResultsThe risk allele G of the polymorphism rs679899 was related to T2D (odds ratio (OR): 1.207, 95% confidence interval (CL): 1.006–1.448, P = 0.043) and the polymorphism rs679899 was associated with glutamyl transpeptidase (GGT) levels (P = 0.001). We also showed that the polymorphism rs6083 was associated with cholesterol (CHOL) levels (P = 0.012), triglyceride (TG) levels (P = 0.040), and low-density lipoprotein cholesterol (LDL) levels (P = 0.033). No significant difference in genotypic frequencies of rs6078 and rs6083 was observed between T2D patients and controls. ConclusionThis study suggests that the APOB polymorphism rs679899 is associated with type 2 diabetes and GGT levels, while the LIPC polymorphism rs6083 may influence CHOL, TG, and LDL levels in Chinese Han population.

Abstract 605: Association of Apolipoprotein B with Impaired Insulin Sensitivity and Secretion Is Mediated by Reduced Fat Clearance in Obese Subjects

OBJECTIVE: Human data from our lab and others have demonstrated that elevated concentrations of apoB-lipoproteins, measured as plasma apoB, are associated with insulin resistance (IR), hyperinsulinemia and the development of type 2 diabetes. However, the underlying mechanism to date remains unknown. We recently reported that LDL, the major form of apoB-lipoproteins, directly impairs the hydrolysis and storage of triglyceride-rich lipoproteins ex vivo in human white adipose tissue. Therefore, we hypothesized that the association between apoB and IR and compensatory increase in insulin secretion (IS) is mediated by delayed postprandial TG clearance in vivo in obese subjects. METHODS: We performed a Botnia clamp on normoglycemic obese men (N=14) and postmenopausal women (N=16) (BMI ≥ 27 kg/m2, age ≥ 45 years). First phase, 2 nd phase and total IS were measured during a 1-hour intravenous-glucose tolerance test (IVGTT) while insulin sensitivity was measured during a 3-hours hyperinsulinemic euglycemic clamp that followed. On a separate date, postprandial plasma clearance of TG was measured over 6 hours following the ingestion of a 13 C-triolein-labeled high-fat meal. RESULTS: Plasma apoB correlated positively with IR (r=0.15, p=0.037), 2 nd phase IS (r=0.15, p=0.039) and delayed TG clearance (AUC 6hrs of total plasma TG: r=0.64, p&lt;0.001; AUC 6hrs of 13 C-plasma TG: r=0.77, p&lt;0.001). Moreover, AUC 6hr of total plasma TG was associated with higher IR (r=0.16, p=0.042), 1 st phase IS (r=0.20, p=0.023), 2 nd phase IS (r=0.16, p=0.044) and total IS (r=0.16, p=0.046). Similarly, a positive association existed between delayed 13 C-labeled plasma TG clearance (AUC 6hrs ) and IR (r=0.41, p=0.046). A gender difference existed as TG clearance was mainly associated with IR in women (r=0.41, p=0.046) whereas it was mainly associated with 2 nd phase IS in men (r=0.41, p=0.046). As hypothesized, correcting for TG clearance eliminated the association of plasma apoB with IR and IS. CONCLUSION: The association of apoB with insulin resistance and secretion may be secondary to LDL-mediated delayed TG clearance by adipose tissue in humans.

Prevalence of chimerism after non-myeloablative hematopoietic stem cell transplantation

Non-myeloablative hematopoietic stem cell transplantation (NMA-HSCT) is performed in onco-hematological patients who cannot tolerate ablative conditioning because of older age or comorbidities. This approach does not completely eliminate host cells and initially results in mixed chimerism. Long-term persistence of mixed chimerism results in graft rejection and relapse. Involvement of graft-versus-host disease is concomitant with complete chimerism and graft-versus-tumor effect. The aim of this study was to evaluate the prevalence of chimerism in onco-hematological patients who underwent NMA-HSCT. Observational clinical study on chimerism status after human leukocyte antigen-identical NMA-HSCT at the Discipline of Hematology and Hemotherapy of Universidade Federal de São Paulo. We sequentially analyzed the amplification of APO-B, D1S80, DxS52, FVW, 33.6, YNZ-2 and H-ras primers using variable number of tandem repeats (VNTR) on 17 pairs and fluorescent in situ hybridization (FISH) with the XY probe and SRY primer on 13 sex-unmatched pairs. The informativeness of the primers using VNTR was 60% for APO-B, 75% D1S80, 36% DxS52, 14% FVW, 40% YNZ-22 and 16% H-ras. The SRY primer was informative in female receptors with male donors. The XY-FISH method was informative in 100% of the sex-unmatched pairs. These methods were sensitive and informative. In VNTR, the association of APO-B with D1S80 showed 88% informativeness. The quantitative FISH method was more sensitive, but had the disadvantage of only being used for sex-unmatched pairs.

The Amino Terminus of Apolipoprotein B Is Necessary but Not Sufficient for Microsomal Triglyceride Transfer Protein Responsiveness

Human apolipoprotein (apo) B mediates the formation of neutral lipid-containing lipoproteins in the liver and intestine. The association of apoB with lipid is thought to be promoted by the microsomal triglyceride transfer protein complex. We have reconstituted lipoprotein assembly in an insect cell line that normally does not support this process. Expression of human microsomal triglyceride transfer protein (MTP) and apolipoprotein B48 (apoB48) together enabled Sf-21 insect cells to secrete approximately 60-fold more lipoprotein-associated triacylglycerol than control cells. This dramatic effect demonstrates that effective partitioning of triacylglycerol into the secretory pathway requires an endoplasmic reticulum-associated neutral lipid transporter (provided by MTP) and an apolipoprotein to shuttle the lipid through the pathway. Expression of the human apoB48 gene in insect cells resulted in secretion of the protein product. Including both MTP subunits with apoB48 and oleic acid specifically increased apoB48 secretion 8-fold over individual subunits alone. To assess whether specific regions of apoB are necessary for MTP responsiveness, nine apoB segments were expressed. These included NH2-terminal segments as well as internal and COOH-terminal regions of apoB fused with a heterologous signal sequence. ApoB segments containing the NH2-terminal 17% of the protein were secreted and responded to MTP activity; however, a segment containing only the NH2-terminal 17% of the protein was not significantly responsive to MTP. Segments lacking the NH2 terminus were not MTP-responsive, and five of six of these proteins were trapped intracellularly but, in certain cases, could be rescued by fusion to apoB17. These results suggest that the NH2 terminus of apoB is necessary but not sufficient for MTP responsiveness.