LIPC

Lipase is an enzyme that catalyzes the breakdown of fats into fatty acids and glycerol, essential for fat digestion and absorption. 

Found in various tissues such as the liver, stomach, fat cells, blood vessels, and small intestine, lipases play crucial roles in lipid metabolism, cholesterol transport, cell signaling, and inflammation. 

LIPC, also known as hepatic triacylglycerol lipase, catalyzes the hydrolysis of triglycerides and phospholipids present in circulating plasma lipoproteins.

LIPC is involved in lipid metabolism and has been studied in relation to serum lipid levels. Research has investigated whether LIPC is associated with serum lipids and whether this gene and serum lipids are independently associated with age-related macular degeneration (AMD).

The LIPC gene has been associated with AMD. Specifically, the HDL-raising allele of the LIPC gene was found to be associated with a reduced risk of AMD.

What is Lipase? [22.] 

Lipase is an enzyme that catalyzes the hydrolysis of fats (lipids), facilitating the breakdown of triglycerides into fatty acids and glycerol. This process is essential for the digestion and absorption of dietary fats as well as fat-soluble vitamins.

Lipases are also involved in cholesterol metabolism and are targeted by certain medications like orlistat, fibrates, and niacin to treat conditions related to fat digestion and cholesterol levels.

Locations of Lipase [22.] 

Lipases are found in various tissues, including the liver (hepatic lipase), stomach (gastric lipase), fat cells (hormone-sensitive lipase), blood vessels (lipoprotein lipase), and the small intestine (pancreatic lipase). 

Functions of Lipase

Functions of lipase may vary slightly depending on the type of lipase concerned. 

General functions of lipase include:

• Fat digestion: it catalyzes the breakdown of triglycerides into fatty acids and glycerol [6., 26.] 

• Lipid metabolism: helps in the processing and transport of dietary lipids [6., 26.] 

• Cell signaling: some lipases are involved in cell signaling pathways [6.] 

• Inflammation: certain lipases play a role in inflammatory processes [3., 8.] 

• Cholesterol transport: Lipoprotein lipase (LPL) plays a critical role in cholesterol metabolism by hydrolyzing triglycerides (TG) in lipoprotein particles, converting them into free fatty acids and glycerol. This process facilitates the uptake of these fatty acids into peripheral tissues for energy storage and consumption. [13., 26.] 

What Does the Enzyme Hepatic Triacylglycerol Lipase Do? [18., 19.]

The LIPC gene encodes hepatic lipase, an enzyme with phospholipase A1 and triglyceride lipase activities. It plays a role in lipid homeostasis, plasma lipoprotein remodeling, and triglyceride breakdown. 

Hepatic lipase converts VLDLs and IDLs to LDLs and assists in transporting high-density lipoproteins (HDLs) that carry cholesterol and triglycerides from the blood to the liver.

In essence, LIPC maintains a balance between LDLs and HDLs, which is crucial for heart disease protection.

Located in the extracellular space, LIPC is implicated in diseases like Alzheimer's, coronary artery disease, familial combined hyperlipidemia, peripheral vascular disease, and type 2 diabetes. [19.]

It acts as a biomarker for hyperinsulinism, obesity, and type 1 diabetes. [19.]

LIPC Deficiency Disorders

Age-Related Macular Degeneration (AMC) [25.] 

The LIPC gene, encoding hepatic lipase, is associated with serum lipid levels and age-related macular degeneration (AMD). 

A genetic variant (T allele) in LIPC is linked to a reduced risk of advanced AMD and higher HDL levels. In a case-control study, higher total cholesterol and LDL levels increased AMD risk, while higher HDL levels tended to reduce it. 

The study suggests that LIPC impacts AMD risk independently of HDL levels, though the mechanisms remain unclear and warrant further investigation.

Cardiovascular Disease Risk [9., 21.]

The LIPC gene, encoding hepatic lipase, is linked to cardiovascular disease (CVD) risk through its role in lipid metabolism. 

A gain-of-function variant (LIPC-E97G) increases hepatic lipase's phospholipase activity, lowering LDL and HDL cholesterol levels. This variant promotes cholesterol-rich lipoprotein remnant clearance by extrahepatic tissues, impacting lipoprotein composition and size. 

While the variant decreases LDL-C levels, its overall effect on atherosclerotic cardiovascular disease (ASCVD) risk requires further investigation. This highlights the importance of hepatic lipase in cholesterol homeostasis and potential therapeutic targeting for CVD.

What is a SNP?

A SNP, or single nucleotide polymorphism, refers to a variation at a single position in a gene along its DNA sequence.  A gene encodes a protein, so an alteration in that gene programs the production of an altered protein.  

As a type of protein with great functionality in human health, alterations in genes for enzymes may confer a difference in function of that enzyme.  The function of that enzyme may be increased or decreased, depending on the altered protein produced.  

SNPs are the most common type of genetic variation in humans and can occur throughout the genome, influencing traits, susceptibility to diseases, and response to medications.

The completion of the Human Genome Project has significantly expanded opportunities for genetic testing by providing a comprehensive map of the human genome that facilitates the identification of genetic variations associated with various health conditions, including identifying SNPs that may cause alterations in protein structure and function.  

Genetic testing for SNPs enables the identification of alterations in genes, shedding light on their implications in health and disease susceptibility.

Specific SNPs Associated with the LIPC Gene

LIPC-E97G [9., 21.]

A novel gain-of-function variant in the LIPC gene, identified as E97G, has been associated with familial combined hypocholesterolemia. 

This variant leads to significantly lower LDL-C and HDL-C levels and has been linked to increased clearance of lipoproteins, impacting lipid metabolism and potentially influencing atherosclerotic cardiovascular disease (ASCVD) development.

Laboratory Testing for LIPC

Genetic testing for single nucleotide polymorphisms (SNPs) typically involves obtaining a sample of DNA which can be extracted from blood, saliva, or cheek swabs. 

The sample may be taken in a lab, in the case of a blood sample.  Alternatively, a saliva or cheek swab sample may be taken from the comfort of home.  

Test Preparation

Prior to undergoing genetic testing, it's important to consult with a healthcare provider or genetic counselor to understand the purpose, potential outcomes, and implications of the test.  This consultation may involve discussing medical history, family history, and any specific concerns or questions. 

Additionally, individuals may be advised to refrain from eating, drinking, or chewing gum for a short period before providing a sample to ensure the accuracy of the test results.  Following sample collection, the DNA is processed in a laboratory where it undergoes analysis to identify specific genetic variations or SNPs. 

Once the testing is complete, individuals will typically receive their results along with interpretation and recommendations from a healthcare professional. 

It's crucial to approach genetic testing with proper understanding and consideration of its implications for one's health and well-being.

Patient-Centric Approaches

A patient-centered approach to SNP genetic testing emphasizes individualized medicine, tailoring healthcare decisions and interventions based on an individual's unique genetic makeup.

When that is combined with the individual’s health status and health history, preferences, and values, a truly individualized plan for care is possible. 

By integrating SNP testing into clinical practice, healthcare providers can offer personalized risk assessment, disease prevention strategies, and treatment plans that optimize patient outcomes and well-being. 

Genetic testing empowers a deeper understanding of genetic factors contributing to disease susceptibility, drug response variability, and overall health, empowering patients to actively participate in their care decisions. 

Furthermore, individualized medicine recognizes the importance of considering socioeconomic, cultural, and environmental factors alongside genetic information to deliver holistic and culturally sensitive care that aligns with patients' goals and preferences. 

Through collaborative decision-making and shared decision-making processes, patients and providers can make informed choices about SNP testing, treatment options, and lifestyle modifications, promoting patient autonomy, engagement, and satisfaction in their healthcare journey.

Genetic Panels and Combinations

Integrating multiple biomarkers into panels or combinations enhances the predictive power and clinical utility of pharmacogenomic testing. Biomarker panels comprising a variety of transporter proteins and enzymes including drug metabolizing enzymes offer comprehensive insights into individual drug response variability and treatment outcomes. 

Combining genetic SNP testing associated with drug transport, metabolism, and pharmacodynamics enables personalized medicine approaches tailored to individual patient characteristics and genetic profiles.

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