Total Lipids In Ldl
Background
Section titled “Background”Lipids are fundamental molecules essential for numerous biological processes, including cell membrane structure, energy storage, and signaling. Within the bloodstream, lipids are transported by lipoprotein particles, which are classified by their density. Low-density lipoprotein (LDL) particles are particularly important for transporting cholesterol and other lipids from the liver to peripheral tissues. Often colloquially referred to as “bad cholesterol,” elevated levels of total lipids carried within LDL particles are a significant and well-established determinant of cardiovascular disease and related health conditions.[1]
Biological Basis
Section titled “Biological Basis”The concentration of total lipids in LDL within the circulation is a complex trait influenced by both environmental factors and genetics. The biological mechanisms governing lipid metabolism, including the synthesis, assembly, transport, and catabolism of LDL particles, involve a vast network of genes and proteins.[1] These processes are highly regulated, but genetic variations can impact their efficiency, leading to individual differences in LDL lipid levels. For instance, some genes regulate the production of apolipoproteins, which are crucial structural components of LDL, while others affect the activity of enzymes involved in lipid processing or the function of receptors responsible for clearing LDL from the blood.
Genetic Contributions
Section titled “Genetic Contributions”Research has shown that circulating lipid levels, including those of LDL, are highly heritable. [1]Genome-wide association studies (GWAS) have been instrumental in identifying numerous common genetic variants, primarily single nucleotide polymorphisms (SNPs), across the human genome that contribute to the variability in total lipids in LDL.[2] These studies have implicated a range of genes and genomic regions, often referred to as loci, in influencing LDL cholesterol concentrations. Examples include genes such as APOB, LDLR, HMGCR, and PCSK9, as well as gene clusters like APOE/APOC and CELSR2-PSRC1-SORT1. [1] Specific variants, like the rs6511720 allele in LDLR or the rs515135 allele in APOB, have been associated with changes in LDL cholesterol levels. [2] Even low-frequency alleles, such as those in PCSK9, can significantly impact LDL cholesterol concentrations. [3] These common genetic factors collectively explain an appreciable portion of the observed differences in LDL cholesterol levels among individuals. [3]
Clinical Relevance
Section titled “Clinical Relevance”Understanding the genetic underpinnings of total lipids in LDL holds significant clinical relevance. Elevated levels are a primary modifiable risk factor for the development and progression of coronary heart disease and other cardiovascular ailments.[1]Genetic insights contribute to a more comprehensive understanding of an individual’s predisposition to dyslipidemia and can help predict their risk for adverse cardiovascular outcomes. While individual common variants may have small effects, their cumulative impact, often contributing to a “polygenic dyslipidemia,” can be substantial.[1] This knowledge can potentially inform personalized medicine approaches, allowing for more targeted risk assessment, early intervention strategies, and the development of novel therapeutic targets.
Social Importance
Section titled “Social Importance”The widespread prevalence of high LDL cholesterol and its strong association with cardiovascular disease makes the study of total lipids in LDL a matter of considerable social importance. Cardiovascular diseases remain a leading cause of morbidity and mortality globally, imposing a substantial burden on healthcare systems and society. Genetic research into LDL lipid levels contributes to public health by improving our ability to identify individuals at higher risk, facilitating population-level screening programs, and supporting educational initiatives about lifestyle modifications. Furthermore, a deeper genetic understanding paves the way for the development of more effective and personalized prevention and treatment strategies, ultimately working towards reducing the global impact of cardiovascular disease.
Limitations
Section titled “Limitations”Population Homogeneity and Generalizability
Section titled “Population Homogeneity and Generalizability”The findings regarding total lipids in ldl are primarily derived from studies predominantly involving individuals of European ancestry, which may limit their direct applicability and generalizability to other populations.[3] For instance, the FHS cohort, a key component of the research, specifically involved Americans of European ancestry, with adjustments made for population substructure within this demographic. [3]This homogeneity means that the genetic variants identified, and their effect sizes, might differ in populations with distinct genetic backgrounds or environmental exposures, potentially leading to varied associations or predictive capabilities for total lipids in ldl.
Furthermore, specific cohort characteristics, such as the examination of ISIS study participants in the early 1990s before lipid-lowering therapies became widespread, while beneficial for avoiding drug confounding, introduces another layer of specificity. [3]This historical context may mean that the insights gained from such a cohort are not entirely reflective of contemporary populations, which may have different lifestyle factors, medical interventions, and demographic profiles. Therefore, cautious interpretation is warranted when extrapolating these results to ethnically diverse or modern clinical settings without further validation.
Phenotype Characterization and Statistical Modeling
Section titled “Phenotype Characterization and Statistical Modeling”The studies focused on measures such as LDL cholesterol and overall lipoprotein concentrations, which are key components of total lipids in ldl, after various statistical adjustments.[3] These adjustments included factors like age, age squared, sex, and ancestry-informative principal components to create standardized residual phenotypes. [3]While crucial for mitigating confounding, this process of residualizing the data could potentially obscure important biological nuances or interactions that contribute to the variability of total lipids in ldl in their raw, unadjusted state.
Moreover, the analyses largely assumed an additive mode of inheritance for SNP effects, which might not fully capture the complexity of genetic architecture for total lipids in ldl.[3] Non-additive effects, such as dominance or epistasis, could play a significant role but would not be detected under this model. Although relatedness among participants was accounted for using sophisticated linear mixed-effects models or variance component-based tests in several cohorts, the underlying assumptions of these models can influence the precise estimation of genetic effects and the overall understanding of genetic contributions. [3]
Unexplored Environmental and Genetic Complexity
Section titled “Unexplored Environmental and Genetic Complexity”A significant limitation lies in the scope of environmental factors considered within the analyses for total lipids in ldl. While adjustments for age and sex were consistently applied, comprehensive data and adjustments for other crucial environmental or lifestyle confounders, such as diet, physical activity levels, smoking status, or socioeconomic factors, were not extensively detailed as part of the primary genetic association analyses.[3]The omission of these variables means that some observed genetic associations might be indirectly influenced or confounded by unmeasured environmental factors, or that gene-environment interactions, which are critical in complex traits like total lipids in ldl, remain largely unexplored.
The studies primarily focused on identifying common genetic variants, leaving a considerable portion of the heritability of total lipids in ldl unexplained by the identified loci. This “missing heritability” suggests that rare variants, structural variations, or more complex genetic interactions not captured by the additive model, along with unmeasured environmental influences, contribute substantially to the phenotypic variation. Therefore, despite the identification of multiple contributing loci, a complete understanding of the genetic and environmental architecture underlying total lipids in ldl requires further investigation into a broader spectrum of genetic variation and environmental exposures.
Variants
Section titled “Variants”Genetic variations play a significant role in determining an individual’s lipid profile, influencing susceptibility to conditions like dyslipidemia and cardiovascular disease. Several genes with diverse functions contribute to the complex regulation of total lipids in low-density lipoprotein (LDL), often through their involvement in lipid synthesis, transport, or breakdown. Understanding these variants helps to clarify the genetic architecture underlying lipid metabolism.
Key regulators of lipid metabolism include genes like LPL, GCKR, and APOB. LPLencodes lipoprotein lipase, a crucial enzyme responsible for breaking down triglycerides in circulating lipoproteins like chylomicrons and very-low-density lipoproteins (VLDL), thereby impacting both triglyceride and high-density lipoprotein (HDL) cholesterol levels.[2] The rs117026536 variant located within or near LPLcan alter the enzyme’s activity or expression, thus affecting the efficiency of triglyceride clearance and indirectly influencing LDL particle composition. Similarly, theGCKRgene, which codes for glucokinase regulator protein, modulates glucokinase activity in the liver, a key step in glucose and lipid homeostasis. Variants such asrs1260326 in GCKRare strongly associated with altered plasma triglyceride levels, reflecting its influence on hepatic lipid synthesis.[2] Furthermore, the APOBgene, encoding apolipoprotein B, is a primary structural component of LDL particles, essential for their formation and metabolism. Thers4665710 variant in the APOB locus can affect the synthesis, secretion, or removal of LDL particles, directly impacting total LDL cholesterol concentrations. [2]
Other genes involved in energy sensing and nutrient response also significantly shape lipid profiles. The MLXIPLgene, also known as ChREBP, encodes a transcription factor that regulates genes involved in glucose and fatty acid synthesis, particularly in response to carbohydrate intake; thus, thers13234131 variant could influence de novo lipogenesis and consequently impact triglyceride and LDL levels .ANGPTL4(Angiopoietin Like 4) directly influences lipid metabolism by inhibiting lipoprotein lipase, which leads to increased plasma triglycerides and potentially affects LDL particle distribution, makingrs116843064 a candidate for influencing these lipid traits . The TOMM40 gene, involved in the mitochondrial protein import machinery, is located in close proximity to the APOE gene, a major determinant of lipid levels. While its primary function is not direct lipid metabolism, the rs61679753 variant could indirectly modulate lipid processing or interact with APOE function to influence LDL cholesterol.
Beyond core metabolic pathways, variants in genes involved in diverse cellular processes like cell adhesion, signaling, and DNA repair can also have indirect yet significant impacts on systemic lipid regulation. For instance, NECTIN2 encodes a cell adhesion molecule crucial for cell-cell interactions, and variants like rs41290120 and rs41289512 could subtly affect cell signaling or tissue integrity relevant to metabolic function . Similarly, ZPR1 is a zinc finger protein involved in RNA binding and cell proliferation, and alterations due to rs964184 might influence broader cellular health or gene expression profiles that indirectly affect lipid homeostasis . The rs174537 variant resides near or within TMEM258, a transmembrane protein, and MYRF, a transcription factor known for its role in myelination; such variants could modulate cellular membrane function or gene regulatory networks impacting metabolic processes. Lastly, TP53BP1 is a key player in the DNA damage response pathway, and the rs150844304 variant could influence cellular stress responses and genomic stability, which are factors increasingly recognized to have systemic metabolic consequences, including impacts on liver function and circulating lipid levels.
Key Variants
Section titled “Key Variants”Classification, Definition, and Terminology
Section titled “Classification, Definition, and Terminology”Definition and Clinical Relevance of LDL Cholesterol
Section titled “Definition and Clinical Relevance of LDL Cholesterol”Low-density lipoprotein cholesterol, often referred to simply as LDL cholesterol, precisely defines the cholesterol content within low-density lipoprotein particles. These particles are integral to systemic lipid transport, primarily responsible for delivering cholesterol from the liver to peripheral cells. Conceptually, LDL cholesterol is a key biomarker for cardiovascular health; however, its clinical significance arises when concentrations are elevated, leading to its deposition in arterial walls—a process known as atherosclerosis. This pathological accumulation is a primary underlying cause of severe cardiovascular events, including myocardial infarction and stroke, making LDL cholesterol a critical determinant of morbidity and mortality worldwide. . These genetic variations can influence the synthesis, breakdown, and transport of lipids and lipoproteins throughout the body. The complex nature of lipid regulation means that many genes interact to determine the overall levels of total lipids found in LDL, rather than a single gene being solely responsible.[3] This polygenic architecture allows for a wide spectrum of individual differences in lipid profiles.
Mechanistic Pathways Involving Apolipoproteins
Section titled “Mechanistic Pathways Involving Apolipoproteins”Specific genetic variants can directly impact the function or abundance of key proteins essential for lipid metabolism, thereby influencing total lipids in LDL. For example, the P446L allele (rs1260326 ) in the GCKRgene has been associated with increased concentrations of apolipoprotein C-III (APOC-III). [3] APOC-III is a protein synthesized in the liver that inhibits the catabolism, or breakdown, of triglycerides, suggesting a mechanism by which this genetic variant can alter lipid processing. Furthermore, variants in the LPA gene, such as the coding SNP rs3798220 , show associations with LDL cholesterol levels and are strongly linked to lipoprotein(a) levels, indicating specific pathways through which genetic factors regulate lipid components relevant to LDL.[3]
Biological Background
Section titled “Biological Background”Understanding LDL and its Role in Lipid Transport
Section titled “Understanding LDL and its Role in Lipid Transport”Low-density lipoprotein (LDL) particles are crucial transporters of lipids, including cholesterol, throughout the bloodstream to various tissues. These lipoproteins are essential for delivering cholesterol to cells for membrane synthesis, steroid hormone production, and other vital cellular functions. However, high concentrations of LDL cholesterol are consistently and compellingly associated with an increased risk of cardiovascular disease (CAD) incidence worldwide.[2] This makes the regulation of total lipids within LDL a significant area of biological and clinical interest, as disruptions in its homeostasis can lead to serious health consequences. The balance of lipid transport and cellular uptake mechanisms plays a critical role in maintaining overall metabolic health.
Molecular Mechanisms of LDL Regulation
Section titled “Molecular Mechanisms of LDL Regulation”The regulation of total lipids in LDL involves a complex interplay of molecular and cellular pathways governing the formation, activity, and turnover of lipoproteins and triglycerides. Key biomolecules, such as apolipoproteins likeAPOB, are fundamental structural components of LDL particles and are crucial for their synthesis and secretion. [2] The primary mechanism for removing LDL from circulation is through the LDLR(low-density lipoprotein receptor), which facilitates cellular uptake; genetic variants nearLDLR are strongly associated with LDL cholesterol levels. [3] Enzymes such as HMGCR play a critical role in cholesterol biosynthesis, affecting the overall pool of cholesterol that can be packaged into LDL particles, and HMGCR has been consistently associated with LDL cholesterol concentrations. [3] Other proteins like PCSK9 regulate LDLR availability by promoting its degradation, thereby influencing circulating LDL levels. [3] Additionally, transcription factors such as MLXIPLactivate triglyceride synthesis, andMAFB interacts with LDL-related proteins, suggesting broader regulatory networks impacting lipid metabolism and LDL composition. [2]
Genetic Basis of LDL Levels
Section titled “Genetic Basis of LDL Levels”Circulating lipid levels, including total lipids in LDL, exhibit high heritability, with numerous genes and their respective proteins implicated in lipid metabolism.[1] Genome-wide association studies (GWAS) have identified multiple genetic loci influencing LDL levels, revealing a polygenic architecture for dyslipidemia. [1] Genes such as APOB, LDLR, HMGCR, and PCSK9have been consistently associated with LDL cholesterol, with specific single nucleotide polymorphisms (SNPs) demonstrating significant effects on concentrations.[3] For instance, an intronic LDLR SNP has been shown to strongly relate to LDL cholesterol, and variants at HMGCR are also robustly linked. [3] Other implicated genes include CELSR2, NCAN, SORT1, and those within clusters like APOE-APOC1-APOC4-APOC2, all contributing to the genetic variation observed in LDL levels within the population. [1]While individually common variants may have small effects, collectively they explain an appreciable fraction of the inter-individual variability in lipoprotein concentrations.[3]
Pathophysiological Consequences of Altered LDL
Section titled “Pathophysiological Consequences of Altered LDL”Elevated levels of total lipids in LDL, particularly LDL cholesterol, are a primary risk factor for the development of coronary artery disease (CAD) and stroke, which are leading causes of morbidity and mortality globally.[2]The underlying pathophysiology is atherosclerosis, a process characterized by the cumulative deposition of LDL cholesterol within artery walls, leading to plaque formation, arterial narrowing, and eventually impaired blood supply to vital organs like the heart and brain.[2]Research indicates a direct correlation where a 1% decrease in LDL cholesterol concentrations can reduce the risk of coronary heart disease by approximately 1%.[2]Genetic variants associated with increased LDL cholesterol concentrations have also been observed to occur at a higher frequency in individuals with CAD, further underscoring the direct pathophysiological link between LDL and cardiovascular health.[2]
Pathways and Mechanisms
Section titled “Pathways and Mechanisms”Lipoprotein Assembly and Receptor-Mediated Uptake
Section titled “Lipoprotein Assembly and Receptor-Mediated Uptake”The regulation of total lipids in low-density lipoprotein (LDL) is intricately linked to the dynamic processes of lipoprotein assembly, secretion, and cellular uptake. Key to this isAPOB, which serves as a structural protein fundamental for the formation and integrity of LDL particles ([2]). These circulating LDL particles are then primarily cleared from the bloodstream through the LDLR, which recognizes APOB on the LDL surface, mediating endocytosis and cellular absorption of cholesterol ([2]). The abundance of LDLR is critically regulated by PCSK9, which promotes the degradation of the receptor, thereby influencing circulating LDL levels. Moreover, the APOE/APOC gene cluster, including APOE, APOC1, APOC4, and APOC2, encodes apolipoproteins that play crucial roles in various stages of lipoprotein metabolism, affecting the binding of lipoproteins to receptors and overall lipid transport ([2]). Variants near SORT1have also been identified, suggesting its role as a potential endocytic receptor for lipoprotein lipase, further influencing LDL metabolism ([2]).
Cholesterol and Triglyceride Metabolic Regulation
Section titled “Cholesterol and Triglyceride Metabolic Regulation”Metabolic pathways governing the synthesis and breakdown of lipids are central to maintaining LDL lipid homeostasis. The cholesterol biosynthesis pathway involves enzymes such as MVK (mevalonate kinase), which catalyzes an early and rate-limiting step in cholesterol production ([2]). Conversely, MMAB is involved in a metabolic pathway responsible for cholesterol degradation, balancing the overall cholesterol pool ([2]). Triglyceride metabolism is tightly controlled by factors likeMLXIPL, a transcription factor that binds to and activates specific motifs in the promoters of triglyceride synthesis genes, thereby increasing triglyceride production ([2]). Lipases such as LPL(lipoprotein lipase),LIPC (hepatic lipase), and LIPG (endothelial lipase) are crucial for the hydrolysis of triglycerides and phospholipids within lipoproteins, affecting the composition and remodeling of LDL ([2]). The activity of these lipases can be modulated by inhibitors like ANGPTL3, which acts as a major regulator of lipid metabolism by inhibiting lipase function, thereby influencing circulating triglyceride and, indirectly, LDL levels ([2]).
Transcriptional and Signaling Control of Lipid Homeostasis
Section titled “Transcriptional and Signaling Control of Lipid Homeostasis”The intricate regulation of lipid metabolism involves extensive transcriptional control and various signaling cascades. Transcription factors like SREBP2 exert significant influence by regulating the expression of genes involved in cholesterol biosynthesis and degradation, including MVK and MMAB ([2]). Similarly, MLXIPLdirectly activates the transcription of genes necessary for triglyceride synthesis, highlighting its role in governing lipid production ([2]). Signaling pathways also contribute to lipid regulation, as evidenced by TRIB1, which encodes a G-protein-coupled receptor-induced protein involved in the regulation of mitogen-activated protein kinases (MAPK), suggesting a potential mechanism for regulating lipid metabolism through this cascade ([2]). Furthermore, specific hepatic nuclear factors, such as HNF4alpha and HNF1alpha, are essential for maintaining hepatic gene expression and lipid homeostasis, while MAFB, a transcription factor, is known to interact with LDL-related protein, indicating its potential role in LDL dynamics ([2]).
Interconnectedness of Lipid Metabolism Pathways
Section titled “Interconnectedness of Lipid Metabolism Pathways”Lipid metabolism functions as a highly integrated system, where pathways regulating different lipid species frequently crosstalk and exhibit hierarchical regulation. Genes involved in lipoprotein metabolism affect the entire cycle of formation, activity, and turnover of lipoproteins and triglycerides ([2]). For instance, variants within the NCANgene are strongly associated with both LDL cholesterol and triglyceride concentrations, indicating a shared regulatory mechanism for these lipid traits ([2]). The APOA5-APOA4-APOC3-APOA1gene cluster exemplifies pathway crosstalk, as these apolipoproteins collaboratively influence triglyceride levels and the metabolism of chylomicrons and very-low-density lipoproteins, thereby impacting the substrate availability for LDL formation ([2]). Similarly, CETP(cholesterol ester transfer protein) facilitates the transfer of cholesterol esters and triglycerides between various lipoproteins, including HDL and LDL, showcasing how a single protein can integrate the dynamics of multiple lipoprotein classes ([2]).
Pathophysiological Implications and Therapeutic Relevance
Section titled “Pathophysiological Implications and Therapeutic Relevance”Dysregulation within these lipid pathways is a major contributor to cardiovascular disease (CVD), highlighting the clinical significance of understanding their mechanisms. Genetic variations influencing lipid levels are strong determinants of cardiovascular morbidity ([2]). For example, a null mutation in human APOC3has been shown to confer a favorable plasma lipid profile and provide apparent cardioprotection, demonstrating how specific genetic alterations can impact disease risk ([2]). The identification of genes like HMGCR, involved in cholesterol biosynthesis, has provided a critical therapeutic target, leading to the development of statins as a primary strategy for preventing cardiovascular risk by lowering circulating cholesterol levels ([2]). Understanding these disease-relevant mechanisms and the complex interplay of genetic factors offers insights into potential new therapeutic targets and strategies for personalizing prevention against dyslipidemia and its associated health outcomes.
Clinical Relevance
Section titled “Clinical Relevance”Risk Assessment and Prognostic Value for Cardiovascular Disease
Section titled “Risk Assessment and Prognostic Value for Cardiovascular Disease”High concentrations of low-density lipoprotein (LDL) cholesterol are consistently and strongly associated with an increased risk of coronary artery disease (CAD), which is a leading cause of morbidity and mortality globally.[2]The fundamental pathology involves the cumulative deposition of LDL cholesterol within the arterial walls, leading to atherosclerosis. This process eventually impairs blood flow, culminating in severe events such as myocardial infarction or stroke.[2]The prognostic significance of LDL cholesterol is further highlighted by quantitative estimates, suggesting that each 1% reduction in LDL cholesterol concentrations can decrease the risk of coronary heart disease by approximately 1%[2]underscoring its critical role in predicting long-term cardiovascular outcomes.
Genetic risk profiles, constructed from loci associated with various lipid traits including LDL cholesterol, offer enhanced capabilities for predicting clinically relevant outcomes such as hypercholesterolemia. Studies demonstrate that integrating a genetic profile into traditional clinical risk assessment, which includes factors like age, sex, and body mass index (BMI), can improve the discriminative accuracy for identifying hypercholesterolemia. This improvement is evidenced by an increase in the Area Under the Receiver-Operating-Characteristic Curve (AUC) from 0.63 to 0.66.[1]This enhancement implies that genetic insights into LDL cholesterol metabolism provide valuable prognostic information, facilitating earlier identification of individuals at high risk for dyslipidemias and subsequent cardiovascular events, thereby guiding more timely preventive strategies.[1]
Genetic Contributions to LDL Levels and Personalized Prevention
Section titled “Genetic Contributions to LDL Levels and Personalized Prevention”Genome-wide association studies (GWAS) have been instrumental in identifying numerous genetic loci that significantly influence LDL cholesterol levels, thereby deepening the understanding of its regulation and pointing towards potential avenues for personalized prevention. Key genes that have been robustly associated with LDL cholesterol include APOB, genes within the APOE/APOC cluster, LDLR, HMGCR, and PCSK9 [2]. [4] Additionally, specific regions near CELSR2, PSRC1, SORT1, NCAN, CILP2, and PBX4 have been identified, each contributing to the polygenic architecture of dyslipidemia [2]. [4]These common genetic variants collectively explain a notable fraction of the inter-individual variability observed in LDL cholesterol concentrations, with a subset of seven single nucleotide polymorphisms (SNPs) contributing an additional 5.7% to the residual variance after accounting for conventional risk factors.[4]
The elucidation of these genetic determinants holds considerable promise for developing more refined and tailored prevention strategies in clinical practice. For instance, certain lower-frequency alleles, such as those within PCSK9, can exert substantial effects on LDL cholesterol levels, altering concentrations by approximately 0.5 standard deviation units. [4]Identifying individuals who carry such variants could enable the implementation of early, targeted interventions, ranging from specific lifestyle modifications to pharmacotherapeutic approaches, potentially even before overt phenotypic manifestations occur.[1]This integration of genetic information with traditional clinical risk factors facilitates a more precise and individualized approach to the prevention of cardiovascular disease.
Clinical Monitoring and Comorbidity Associations
Section titled “Clinical Monitoring and Comorbidity Associations”Monitoring LDL cholesterol levels is a fundamental aspect of clinical practice for the effective management and prevention of cardiovascular diseases. The established normal range for LDL cholesterol typically falls between 60–129 mg/dl, with values outside this range indicating potential dyslipidemia and an elevated risk of cardiovascular events.[5]Elevated LDL cholesterol is intricately linked to the initiation and progression of atherosclerosis, which serves as the primary underlying pathology for significant comorbidities such as myocardial infarction and stroke.[2] Consequently, the regular assessment of LDL cholesterol acts as a crucial diagnostic tool and guides the intensity of preventive and therapeutic interventions.
Effective management of LDL cholesterol is essential in mitigating the long-term complications associated with dyslipidemia. Key prevention strategies in clinical practice include screening for increased circulating lipid levels and initiating early treatment, often involving statins. [1] Furthermore, dietary modifications are recognized as a foundational primary prevention strategy at the population level. [1] The incorporation of genetic risk scores, particularly those related to LDL cholesterol, into comprehensive risk assessments can further enhance the precision of treatment selection and monitoring strategies, especially for individuals presenting with complex or overlapping lipid disorder phenotypes.
References
Section titled “References”[1] Aulchenko, Y. S. et al. “Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.”Nat Genet, vol. 40, no. 2, 2008, pp. 161–169.
[2] Willer, C. J. et al. “Newly identified loci that influence lipid concentrations and risk of coronary artery disease.”Nat Genet, vol. 40, no. 2, 2008, pp. 161–169.
[3] Kathiresan, S. “Common variants at 30 loci contribute to polygenic dyslipidemia.” Nat Genet, 2008. PMID: 19060906.
[4] Kathiresan S et al. “Common variants at 30 loci contribute to polygenic dyslipidemia.” Nat Genet, PMID: 19060906.
[5] Ober, C., et al. “Genome-wide association study of plasma lipoprotein(a) levels identifies multiple genes on chromosome 6q.”Journal of Lipid Research, 2009.