Apolipoprotein B
Apolipoprotein B (ApoB) is a fundamental protein involved in the transport of lipids throughout the body. It serves as a primary structural component of several lipoprotein particles, including very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and low-density lipoproteins (LDL), as well as chylomicrons. These lipoproteins are responsible for carrying fats, such as cholesterol and triglycerides, in the bloodstream to various tissues.
Biological Basis
Section titled “Biological Basis”The human body produces two main forms of apolipoprotein B: ApoB-100 and ApoB-48. ApoB-100 is synthesized in the liver and is found on VLDL, IDL, and LDL particles. Each LDL particle, often referred to as “bad cholesterol,” contains precisely one molecule of ApoB-100. This characteristic makes ApoB a direct indicator of the total number of these potentially atherogenic lipoprotein particles in circulation. ApoB-48, on the other hand, is produced in the intestines and is a component of chylomicrons, which transport dietary fats from the digestive system. The level of apolipoprotein B in plasma can be determined using methods such as enzyme-linked immunosorbent assay (ELISA).[1]Genetic variations, including single nucleotide polymorphisms (SNPs), in genes that influence lipid metabolism, such asAPOE, can significantly impact plasma lipid and lipoprotein levels.[2]
Clinical Relevance
Section titled “Clinical Relevance”Elevated levels of apolipoprotein B are a significant risk factor for cardiovascular diseases, including atherosclerosis and coronary heart disease. A higher concentration of ApoB indicates a greater number of circulating atherogenic particles, which can infiltrate the arterial walls and contribute to the formation of plaque. For this reason, ApoB is often considered a more comprehensive marker of cardiovascular risk than LDL cholesterol alone, particularly in individuals with conditions like metabolic syndrome or diabetes, or those with normal LDL cholesterol but high triglycerides. Genome-wide association studies (GWAS) have identified numerous genetic loci that influence lipid concentrations and the risk of coronary artery disease, highlighting the complex interplay between genetics and lipid metabolism.[3] These studies leverage large datasets from cohorts such as the Framingham Heart Study.[4] and utilize high-density SNP platforms for genotyping.[5]
Social Importance
Section titled “Social Importance”Cardiovascular diseases remain a leading global health concern, necessitating effective strategies for risk assessment, prevention, and treatment. The ability to accurately assess apolipoprotein B levels provides a valuable tool for clinicians to better identify individuals at higher risk of these conditions. Understanding the genetic factors that influence ApoB levels can contribute to the development of more personalized medical approaches, potentially leading to earlier interventions and improved public health outcomes.
Methodological and Phenotypic Considerations
Section titled “Methodological and Phenotypic Considerations”The interpretation of apolipoprotein B findings can be influenced by the methodologies used for related lipid measurements. For instance, low-density lipoprotein cholesterol (LDL-C) levels were determined using the Friedewald formula, a calculation method rather than a direct.[6]This approach may introduce inaccuracies, particularly in individuals with high triglyceride levels, potentially affecting the precision with which the true burden of apolipoprotein B-carrying particles is assessed. Consequently, any downstream genetic associations or risk predictions related to apolipoprotein B, if inferred from such calculated values, could be subject to error.
While specific details on apolipoprotein B itself are not provided in the context, other crucial biomarkers likeApoE levels were determined via specific analytical platforms such as ELISA.[6]The choice of assay, its inherent variability, and the degree of inter-laboratory standardization are critical factors that can impact the reliability and comparability of results. Such technical nuances in biomarker quantification can affect the accuracy of phenotypic characterization, which is fundamental for robust genetic association studies and for understanding the complex interplay between genetic variants and apolipoprotein B metabolism.
Statistical Power and Generalizability
Section titled “Statistical Power and Generalizability”Studies often face limitations in statistical power due to moderate cohort sizes, which can lead to false negative findings where genuine, albeit modest, associations with apolipoprotein B or related traits are overlooked.[7]This lack of power makes it challenging to detect subtle genetic effects that might still hold clinical significance, thereby providing an incomplete picture of the genetic landscape influencing apolipoprotein B. Conversely, the extensive number of comparisons inherent in genome-wide association studies (GWAS) heightens the risk of false positive associations.[7] These spurious findings can inflate reported effect sizes and require rigorous replication in independent and sufficiently powered cohorts, which is not always feasible or successful, thus contributing to replication gaps in the literature.
The applicability of genetic findings to broader populations is also a significant concern, as studies may suffer from cohort bias. If the investigated populations primarily represent a specific ancestry or demographic, the identified genetic variants influencing apolipoprotein B may not generalize to other ethnic groups, potentially missing ancestry-specific genetic factors or gene-environment interactions. This restricted generalizability underscores the need for diverse study populations to fully elucidate the genetic architecture of apolipoprotein B across human populations.
Remaining Knowledge Gaps and Confounding Factors
Section titled “Remaining Knowledge Gaps and Confounding Factors”Despite considerable research, a substantial portion of the heritability for complex traits like apolipoprotein B levels remains unexplained, highlighting a “missing heritability” challenge. This suggests that current genetic studies may not fully capture all contributing factors, including the influence of rare genetic variants, complex epigenetic modifications, or gene-gene interactions that modulate apolipoprotein B. Furthermore, environmental or gene-environment confounders, such as diet, lifestyle, and co-morbidities, can significantly impact apolipoprotein B levels. Without comprehensive data on these factors, disentangling their precise contributions from genetic influences remains challenging, leading to knowledge gaps in the complete etiology of apolipoprotein B regulation and its clinical implications.
Variants
Section titled “Variants”Genetic variations play a crucial role in influencing apolipoprotein B (ApoB) levels and overall lipid metabolism, which are key indicators for cardiovascular health. Variants within theAPOB gene itself, such as rs533617 , rs673548 , and rs550619 , can directly impact the structure or expression of ApoB, the primary protein component of low-density lipoprotein (LDL) particles. High ApoB levels generally reflect a greater number of circulating atherogenic lipoprotein particles, thus increasing the risk of cardiovascular disease. TheAPOB gene is strongly associated with LDL cholesterol levels, as evidenced by significant associations found in genome-wide association studies.[3] Similarly, the LDLR gene, which encodes the LDL receptor responsible for clearing LDL particles from the bloodstream, also harbors variants like rs72658867 , rs6511721 , and rs6511720 that can affect receptor efficiency. Reduced LDLR function leads to higher circulating LDL cholesterol and ApoB levels, a finding consistently observed in studies of lipid concentrations.[3] Additionally, variants rs12691088 and rs389261 in the APOC1 gene, part of the APOE/APOC gene cluster, are also implicated in LDL cholesterol regulation and thus indirectly ApoB.
Other genes significantly influence lipid profiles, including those affecting high-density lipoprotein (HDL) and triglycerides, which can also have downstream effects on ApoB. For instance, theCETPgene, which codes for cholesteryl ester transfer protein, is a major determinant of HDL cholesterol levels, with variants likers183130 , rs821840 , and rs3764261 being linked to its activity. Modulations in CETP activity can alter the transfer of cholesteryl esters and triglycerides between lipoproteins, thereby influencing the composition and clearance of ApoB-containing particles.[3] The TRIB1 gene, represented by variants such as rs28601761 , rs2954038 , and rs2954021 , plays a role in triglyceride metabolism and has been consistently associated with triglyceride levels.[3]Changes in triglyceride levels often correlate with changes in very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) particles, both of which contain ApoB, thus impacting total ApoB.
Beyond these core lipid-regulating genes, other genetic regions contribute to the complex interplay of lipid metabolism. Variants in genes like NECTIN2 (rs41289512 , rs144261139 , rs3852856 ), APOC1P1 (rs7259350 , rs60049679 , rs71352239 ), and TOMM40 (rs76366838 , rs61679753 , rs75687619 ) may exert more subtle influences on lipid pathways or are in linkage disequilibrium with other causal variants. For instance, TOMM40 is located near the APOEgene and has been associated with lipid traits and Alzheimer’s disease risk. TheHERPUD1 gene, often discussed in conjunction with CETP, along with variants in the TDRD15 - NUTF2P8 region (rs10166144 , rs79355265 , rs116157399 ) and the ZNF285 gene (rs62116778 ), represent additional genetic loci that contribute to the polygenic architecture of lipid traits and, by extension, apolipoprotein B concentrations. These genes might be involved in diverse cellular processes, including protein degradation, RNA processing, or other metabolic pathways that indirectly affect lipoprotein synthesis, modification, or clearance.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs533617 rs673548 rs550619 | APOB | apolipoprotein A 1 apolipoprotein b triglyceride:HDL cholesterol ratio total cholesterol triglyceride |
| rs41289512 rs144261139 rs3852856 | NECTIN2 | family history of Alzheimer’s disease Alzheimer disease, family history of Alzheimer’s disease Alzheimer disease apolipoprotein A 1 apolipoprotein b |
| rs7259350 rs60049679 rs71352239 | APOC1P1, APOC1P1 | apolipoprotein b fatty acid amount omega-3 polyunsaturated fatty acid |
| rs76366838 rs61679753 rs75687619 | TOMM40 | apolipoprotein A 1 apolipoprotein b aspartate aminotransferase to alanine aminotransferase ratio C-reactive protein total cholesterol |
| rs183130 rs821840 rs3764261 | HERPUD1 - CETP | high density lipoprotein cholesterol metabolic syndrome total cholesterol low density lipoprotein cholesterol , phospholipids:total lipids ratio intermediate density lipoprotein |
| rs28601761 rs2954038 rs2954021 | TRIB1AL | mean corpuscular hemoglobin concentration glomerular filtration rate coronary artery disease alkaline phosphatase YKL40 |
| rs10166144 rs79355265 rs116157399 | TDRD15 - NUTF2P8 | apolipoprotein b total cholesterol low density lipoprotein cholesterol |
| rs62116778 | ZNF285 | apolipoprotein A 1 apolipoprotein b total cholesterol low density lipoprotein cholesterol non-high density lipoprotein cholesterol |
| rs12691088 rs389261 | APOC1 | serum alanine aminotransferase amount apolipoprotein A 1 apolipoprotein b aspartate aminotransferase to alanine aminotransferase ratio C-reactive protein |
| rs72658867 rs6511721 rs6511720 | LDLR | apolipoprotein b total cholesterol low density lipoprotein cholesterol Hypercholesterolemia coronary artery disease |
Clinical Evaluation and Biochemical Quantification
Section titled “Clinical Evaluation and Biochemical Quantification”Apolipoprotein B (apoB) is a crucial diagnostic tool in the assessment of lipid profiles and cardiovascular risk. Clinically, elevated apolipoprotein B concentrations are indicative of an increased number of atherogenic lipoprotein particles, which include low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and lipoprotein(a) [Lp(a)]. Direct quantification of plasma apolipoprotein B can be achieved through methods such as the enzyme-linked immunosorbent assay (ELISA), which provides a precise measure of the apolipoprotein B protein itself.[1]This direct offers advantages over calculated low-density lipoprotein cholesterol (LDL-C) estimations, such as the Friedewald equation, particularly in cases of hypertriglyceridemia where LDL-C calculations may be less accurate.[8]The clinical utility of apolipoprotein B lies in its ability to serve as a comprehensive marker for the total burden of atherogenic lipoproteins, aiding in the identification of individuals at higher risk for atherosclerotic cardiovascular disease, even when traditional lipid parameters might appear borderline.
Genetic and Molecular Markers
Section titled “Genetic and Molecular Markers”Genetic testing and molecular markers play an increasingly important role in understanding the determinants of apolipoprotein B levels and associated dyslipidemias. Genome-wide association studies (GWAS) have successfully identified numerous genetic loci that influence lipid concentrations, including those directly impacting apolipoprotein B and LDL-cholesterol levels, thereby contributing to the risk of coronary artery disease.[3] For instance, specific loci influencing overall lipid levels and LDL-cholesterol concentrations have been discovered through broad population studies.[3] Furthermore, variations in genes such as APOEhave been linked to plasma C-reactive protein levels and LDL-cholesterol concentrations, highlighting the complex interplay of genetic factors in lipid metabolism and inflammation.[9]These genetic insights provide a deeper understanding of individual predispositions to dyslipidemia and cardiovascular risk, complementing biochemical measurements by identifying genetic variants that quantitatively or qualitatively affect plasma lipid components.
Differential Diagnosis and Risk Stratification
Section titled “Differential Diagnosis and Risk Stratification”Apolipoprotein B is pivotal in refining differential diagnosis and risk stratification for cardiovascular disease, especially when distinguishing between various forms of dyslipidemia. Unlike LDL-cholesterol, which measures the amount of cholesterol within LDL particles, apolipoprotein B directly reflects the number of atherogenic particles, offering a more accurate assessment of risk in conditions such as familial combined hyperlipidemia, diabetes, or metabolic syndrome where LDL particle number may be disproportionately high relative to LDL-cholesterol. This helps differentiate individuals who may have normal or near-normal LDL-C but still carry a significant burden of small, dense, highly atherogenic LDL particles. By providing a direct count of these particles, apolipoprotein B aids clinicians in precisely characterizing the atherogenic risk profile, guiding more targeted therapeutic interventions and improving the accuracy of cardiovascular risk prediction beyond standard lipid panels.
Biological Background
Section titled “Biological Background”The researchs materials do not contain specific information about apolipoprotein B.
Metabolic Regulation of Apolipoprotein Dynamics
Section titled “Metabolic Regulation of Apolipoprotein Dynamics”The circulating levels of apolipoproteins, including those associated with apolipoprotein B, are intricately linked to metabolic pathways that govern lipid synthesis, transport, and catabolism. Apolipoproteins play a crucial role in the packaging and movement of triglycerides and cholesterol throughout the body. For instance, an apolipoprotein identified through comparative sequencing has been shown to influence triglyceride levels in both humans and mice, highlighting its significant role in lipid metabolism.[10]This metabolic regulation involves the coordinated action of enzymes, transporters, and regulatory proteins that ensure proper flux control and energy partitioning, impacting the formation and clearance of lipoprotein particles. Dysregulation within these pathways can lead to altered lipid profiles, contributing to conditions like hypertriglyceridemia, which is strongly associated with coronary disease.[11]
Genetic and Transcriptional Control of Apolipoprotein Expression
Section titled “Genetic and Transcriptional Control of Apolipoprotein Expression”The production and modification of apolipoproteins are tightly controlled at the genetic and post-translational levels. Gene regulation dictates the quantity of apolipoproteins synthesized, with specific genetic variants influencing circulating protein levels. For example, variants in the APOA5gene region are known to influence triglyceride levels and can affect the response to lipid-modifying therapies, demonstrating a direct link between genotype and metabolic phenotype.[12] Similarly, genetic variations within the APOE gene are associated with differences in plasma LDL-cholesterol levels and the overall concentration of apoE protein itself.[13] Beyond transcriptional control, post-translational modifications and allosteric regulation further fine-tune apolipoprotein function and stability, influencing their interactions with lipids and cellular receptors.
Signaling and Systemic Integration in Lipid Homeostasis
Section titled “Signaling and Systemic Integration in Lipid Homeostasis”Apolipoprotein metabolism is not an isolated process but is deeply integrated with broader physiological signaling networks. These pathways involve receptor activation and intracellular cascades that respond to metabolic cues, regulating lipid synthesis, uptake, and secretion. For example, apolipoproteins are also implicated in immune functions, such as the apolipoprotein-mediated pathways involved in lipid antigen presentation, showcasing a complex interplay between lipid metabolism and the immune system.[14] Furthermore, pathway crosstalk extends to other metabolic systems; variants in genes like MTNR1B, which encodes the melatonin receptor 1B, have been associated with alterations in fasting glucose levels, illustrating how seemingly disparate signaling pathways can collectively influence overall metabolic health and indirectly impact lipid homeostasis.[15]
Apolipoprotein Dysregulation and Disease Pathogenesis
Section titled “Apolipoprotein Dysregulation and Disease Pathogenesis”Alterations in apolipoprotein pathways are fundamental to the pathogenesis of numerous metabolic diseases. Dysregulation in the synthesis, assembly, or catabolism of apolipoproteins can lead to imbalanced lipid profiles, contributing to chronic conditions. For instance, triglyceride-mediated pathways are recognized as significant contributors to coronary disease, underscoring the clinical importance of maintaining apolipoprotein balance.[11] Specific genetic polymorphisms, such as those within the APOE gene, are established risk factors for metabolic syndrome and are strongly linked to an increased risk of coronary events.[16]Understanding these disease-relevant mechanisms provides critical insights for identifying compensatory pathways and developing targeted therapeutic strategies aimed at restoring lipid homeostasis and mitigating disease progression.
Frequently Asked Questions About Apolipoprotein B
Section titled “Frequently Asked Questions About Apolipoprotein B”These questions address the most important and specific aspects of apolipoprotein b based on current genetic research.
1. Can I have ‘good’ cholesterol but still have high ApoB risk?
Section titled “1. Can I have ‘good’ cholesterol but still have high ApoB risk?”Yes, absolutely. You can have seemingly normal LDL cholesterol levels but still have a higher number of dangerous cholesterol-carrying particles. ApoB directly counts these particles, which can infiltrate arterial walls and cause plaque. This is why ApoB is often a more accurate indicator of your heart disease risk, especially if you have conditions like diabetes or high triglycerides.
2. Does my family history mean I’ll have high ApoB?
Section titled “2. Does my family history mean I’ll have high ApoB?”Yes, your family history can play a significant role. Genetic variations, like those in the APOEgene, can affect how your body processes fats and lead to higher ApoB levels. While lifestyle is crucial, a strong family history of heart disease suggests you might have a genetic predisposition, making regular ApoB checks even more important for you.
3. I eat healthy and exercise; why might my ApoB still be high?
Section titled “3. I eat healthy and exercise; why might my ApoB still be high?”Even with a healthy lifestyle, your ApoB levels can be influenced by your genetics. Some people have inherited predispositions that affect how their bodies manage lipids, leading to higher ApoB regardless of diet and exercise. This highlights the complex interplay between your genes and your environment, and why personalized medical approaches are valuable.
4. I have diabetes, why is ApoB more important for my heart?
Section titled “4. I have diabetes, why is ApoB more important for my heart?”If you have diabetes or metabolic syndrome, ApoB is particularly crucial because these conditions often involve abnormal lipid profiles, like high triglycerides. In these cases, your LDL cholesterol might not fully capture your risk, but ApoB provides a more direct count of the dangerous particles that can lead to plaque buildup and heart disease.
5. Should I ask my doctor to check my ApoB levels?
Section titled “5. Should I ask my doctor to check my ApoB levels?”It’s a good conversation to have with your doctor, especially if you have a family history of heart disease, metabolic syndrome, diabetes, or if your regular cholesterol tests show high triglycerides. ApoB offers a more comprehensive view of your cardiovascular risk than LDL cholesterol alone, helping to guide personalized prevention strategies.
6. Does my ApoB naturally go up as I get older?
Section titled “6. Does my ApoB naturally go up as I get older?”While the article doesn’t explicitly detail age-related changes in ApoB, lipid metabolism can shift as you age, potentially influencing your ApoB levels. Regular monitoring of your lipid profile, including ApoB, becomes increasingly important with age to proactively manage your cardiovascular health risks.
7. Does my ethnic background affect my ApoB risk?
Section titled “7. Does my ethnic background affect my ApoB risk?”Yes, your ethnic background can influence your ApoB risk. Genetic studies show that certain genetic variants influencing lipid levels and heart disease risk can vary across different ancestries. This means that risk factors or protective factors for ApoB might be different depending on your specific demographic background.
8. If I eat a lot of fatty foods, how quickly does that affect my ApoB?
Section titled “8. If I eat a lot of fatty foods, how quickly does that affect my ApoB?”When you eat fatty foods, your intestines produce ApoB-48 as part of chylomicrons to transport those dietary fats. The liver also produces ApoB-100 on VLDL particles, which carry fats synthesized in the body. So, your diet has a direct and relatively quick impact on the fat-carrying particles in your bloodstream, influencing your overall ApoB levels.
9. My sibling has high ApoB, but I don’t. Why the difference?
Section titled “9. My sibling has high ApoB, but I don’t. Why the difference?”Even within families, there can be differences in ApoB levels due to a combination of unique genetic variations and lifestyle choices. While you share some genes, individual genetic predispositions (like specific SNPs) can vary, and environmental factors such as diet, exercise, and other habits also play a significant role in determining each person’s ApoB profile.
10. Can knowing my ApoB help me prevent heart disease?
Section titled “10. Can knowing my ApoB help me prevent heart disease?”Absolutely. Knowing your ApoB level is a powerful tool for preventing heart disease. It provides a more precise measure of your risk by directly counting the atherogenic particles. This information allows your doctor to recommend more personalized interventions, such as specific diet changes, exercise routines, or medications, to lower your risk proactively.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
Section titled “References”[1] Ordovas, J. M., et al. “Enzyme-linked immunosorbent assay for human plasma apolipoprotein B.”J Lipid Res, vol. 28, 1987, pp. 1216–1224.
[2] Sing, C. F., and J. Davignon. “Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation.”Am J Hum Genet, vol. 37, 1985, pp. 268-85.
[3] Willer, C. J., et al. “Newly identified loci that influence lipid concentrations and risk of coronary artery disease.”Nat Genet, vol. 40, 2008, pp. 161-9.
[4] Cupples, L. A., et al. “The Framingham Heart Study 100K SNP genome-wide association study resource: overview of 17 phenotype working group reports.” BMC Med Genet, vol. 8, Suppl 1, 2007, p. S1.
[5] Grallert, H., et al. “Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies.”Eur Heart J, 2012.
[6] Deelen, J., et al. “Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited.” Aging Cell, vol. 10, no. 4, 2011, pp. 686-698.
[7] Benjamin, E. J., et al. “Genome-wide association with select biomarker traits in the Framingham Heart Study.” BMC Medical Genetics, vol. 8, 2007, p. 58.
[8] Friedewald, WT, et al. “Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.”Clin Chem, vol. 18, no. 6, 1972, pp. 499-502.
[9] Judson, R., et al. “New and confirmatory evidence of an associ-ation between APOEgenotype and baseline C-reactive protein in dyslipidemic individuals.”Atherosclerosis, vol. 177, no. 2, 2004, pp. 345-351.
[10] Pennacchio LA, Olivier M, Hubacek JA, Cohen JC, Cox DR, et al. “An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.” Science, vol. 294, 2001, pp. 169–173.
[11] Sarwar N, Sandhu MS, Ricketts SL, Butterworth AS, Di AE, et al. “Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies.”Lancet, vol. 375, 2010, pp. 1634–1639.
[12] Girona J, Guardiola M, Cabre A, Manzanares JM, Heras M, Ribalta J, Masana L. “The apolipoprotein A5 gene 1131T/Cpolymorphism affects vitamin E plasma concentrations in type 2 diabetic patients.”Clin. Chem. Lab. Med., vol. 46, 2008, pp. 453–457.
[13] Bennet AM, Di Angelantonio E, Ye Z, Wensley F, Dahlin A, Ahlbom A, Keavney B, Collins R, Wiman B, de Faire U, Danesh J. “Association of apolipoprotein E genotypes with lipid levels and coronary risk.”JAMA, vol. 298, 2007, pp. 1300–1311.
[14] van den Elzen P, Garg S, Leon L, Brigl M, Leadbetter EA, Gumperz JE, Dascher CC, Cheng TY, Sacks FM, Illarionov PA, et al. “Apolipoprotein-mediated pathways of lipid antigen presentation.” Nature, vol. 437, 2005, pp. 906–910.
[15] Holzapfel C, Siegrist M, Rank M, Langhof H, Grallert H, et al. “Association of a MTNR1Bgene variant with fasting glucose and HOMA-B in children and adolescents with high BMI-SDS.”Eur J Endocrinol, vol. 164, 2011, pp. 205–212.
[16] Sima A, Iordan A, Stancu C. “Apolipoprotein E polymorphism–a risk factor for metabolic syndrome.”Clin. Chem. Lab. Med., vol. 45, 2007, pp. 1149–1153.