Can Hyperlipidemia be Inherited

Introduction

Hyperlipidemia, better known to patients as high cholesterol, is a common problem and can refer to any number of physical disorders that result from extra fats (lipids) in the blood.  Lipids commonly associated with this disease are cholesterol and triglycerides.  These fats will deposit in the walls of blood vessels are restrict blood flow, which can lead to heart attack or stroke.  There are no symptoms of hyperlipidemia and the disease is only identified after the fact (following a stroke or heart attack) or through routine testing of blood.  There are more than 3 million cases per year of hyperlipidemia (Mayo Clinic, 2017).

Phenotype and Genotype

Familial combined hyperlipidemia lipid phenotype and ApoE E2/E2 genotype have been used to identify the disease; determining the lipoprotein levels is important.  The lipoprotein profile should be determined by examining LDL-C, HDL-C, TG, and total cholesterol) following a 9 hour fast.  Physicians may particularly look for “elevated apolipoprotein B (apoB) levels and the presence of small dense low density lipoprotein (LDL), as reflected by a low value of the parameter K (apoB 1461±305 versus 997±249 mg/L, respectively [P<0.001]; K value ?0.22±0.19 versus ?0.02±0.19, respectively [P<0.001])” in the patient (Veerkamp, de Graaf, Bredie et al., 2002, p. 274).

Pathophysiological Processes

The pathophysiological processes of hyperlipidemia begin with elevated plasma LDL, which leads to the penetration of native LDL-C particles via endothelium and into the intimal layer of the arterial wall.  LDL-C particles are oxidized (which causes the discharge of chemotactic factors, such as cytokines).  Macrophages in the intima consume the oxidized LDL-C to create foam cells.

Lesions then form (the foam cells form the early atherosclereotic lesion), leading to fissures and aggregation of the platelet, which causes thrombin generation.  Formation of fibrin results and the thrombus is impacted, with occlusion potentially resulting, manifesting itself as acute coronary syndrome.  Endothelial cells discharge glycoproteins which lead to monocyte adhesion to the endothelial surface.

The oxidization of the LDL-C causes the endothelial cells to create chemotactic factor and cytokines.  Monocytes penetrate the intima and differentiate into macrophages.  Macrophages then produce growths—smooth muscle cells proliferate, which leads to a fatty streak.

Genetic Predispositions and Tendencies

The genetic predispositions of hyperlipidemia include familial combined hyperlipidemia (FCHL) in the patient’s relatives (Aguilar-Salinas, Díaz-Polanco, Quintana, 2002).  Additionally, “single-gene mutations in apoproteins, lipoproteins, and some of the enzymes involved in lipoprotein may underlie” causation of hyperlipidemia in individuals (Nestruck, Davignon, 1986, p. 47).  However, any clear identification of genetic predisposition is uncertain because there are a variety of genes that can lead to the cause of the disease.

Genetic tendencies of individuals at risk of hyperlipidemia include autosomal dominant disorder, triggered by mutations in the LDL receptor gene 4.  Familial defective apoplipoprotein B is a gene that can lead to the mutation of codon 3500 in apoB gene 5 and can be inherited from first-degree relatives.  This gene has a dominant inheritance, which means that individuals can pass it on to offspring.  Single gene defects are significant since they lead to high plasma cholesterol and are associated with cardiovascular disease (Beilby, 2005).

Patterns of Inheritance

If hyperlipidemia is produced by mutations in LDLRAP1 gene, the disease is viewed as being inherited through autosomal recessive pattern.  This means that recessive inheritance is the result of two changed copies of the gene in each cell, the two parents of the person each carrying a copy of the changed gene.  Normally, inherited forms of hyperlipidemia stem from changes in the APOB, LDLR, and PCSK9 genes, which indicate autosomal dominant pattern inheritance.  In such cases, only a single copy of a changed gene in each cell is responsible for the disease.  In other words, the gene is passed on to the person from only one parent., while the other parent passes on a normal copy of the gene (NIH, 2017).

Genetic Basis of the Phenotype

LDL receptor gene mutations typically account for the genetic basis of the phenotype.  However, there are other expressions that can be identified if this mutation is not evident, such as the autosomal dominant inherited gene.  Typically heterozygotes are the inheritors of hyperlipidemia, with 10 million people worldwide identified as having the disease (Castro-Oros, Pocovi, Civeira, 2010).  Most commonly the mutation is the LDLR protein, though apolipoprotein B and proprotein convertase subtilisin/kexin type 9 genes also produce this phenotype (Castro-Oros et al., 2010).

Genetic Mutation

Thus, there is clearly a genetic mutation that has been found to produce this disease, and there are a variety of mutations that have been linked to hyperlipidemia over the years by researchers.  However, the disease is not always linked to genetic mutation and hyperlipidemia can be caused by environmental factors, such as diet and exercise and how the patient’s lifestyle is led.  Therefore, hyperlipidemia may result from genetic mutation but is not required to stem from this mutation (Castro-Oros et al., 2010).

Current Research

Current research on hyperlipidemia includes testing interventions, treatments, and long-term risks associated with the disease.  Researchers have conducted longitudinal analysis of young patients with hyperlipidemia and the risk of coronary heart disease developing later in life.  They have examined the risks and benefits of using Statin Therapy as a treatment for hyperlipidemia.  There are also numerous studies in which a variety of pharmacological interventions are tested to assess their impact on hyperlipidemia.

Racial and Ethnic Predispositions

While African-Americans suffer from more fatalities as a result of cardiovascular disease stemming from hyperlipidemia, it is more likely that these deaths are the result of risk factor clustering and less the result of hyperlipidemia in particular.  White Caucasians actually are predisposed to having worse lipids than Blacks in terms of how the body physically handles the lipid level increases.  With Hispanics, there is a difference in general levels of lipids as well; thus, it is too simplistic to say that some racial or ethnic groups are predisposed to hyperlipidemia based on their race or ethnicity. The reality is that there are many external factors that may play a role in the onset of the disease.

Risk of Development

The risk of development is high among individuals who do not eat a healthy, organic diet, and who do not exercise. The body responds to environmental pressures and excess fat levels can lead to hyperlipidemia as a result of diet and lack of exercise.  Persons who are older in age may experience a higher degree of risk.

Interdisciplinary Management Plan

Statins, injectible medications, cholesterol absorption inhibitors, fibrates, niacin, omega-3 fatty acid supplements, diet free of animal fat, and exercise can all be used as a part of an interdisciplinary management plan to treat hyperlipidemia.  Exercise and diet can help as preventive methods of treatment and management, while medications can be used to reduce the strain after the fact.