ABCC8

ABCC8 is a gene encoding the ATP-binding cassette transporter subfamily C member 8 protein, which functions as a regulatory subunit of the pancreatic beta-cell ATP-sensitive potassium channel involved in insulin secretion and glucose homeostasis.

It offers a window into understanding complex disease mechanisms, potentially leading to more accurate diagnoses and personalized treatment strategies. 

As we dive deeper into the realm of personalized medicine, where treatments are tailored to the individual characteristics of each patient, genetic testing for genes like ABCC8 become invaluable. 

What is ABCC8?  [1., 6.]

ABCC8, or ATP-Binding Cassette Subfamily C Member 8, is a gene that codes for the SUR1 (sulfonylurea receptor 1) subunit of the potassium-dependent ATP (KATP) channel.  The SUR1 subunits bind sulfonylureas, which induce insulin secretion by having an inhibitory effect on the KATP channel), and diazoxide, which stops insulin release by opening the KATP channel.  [7.]

This channel, predominantly found in the pancreas and heart, plays an instrumental role in connecting metabolic signals with cellular activities. 

In the pancreas, ABCC8 is directly involved in the regulation of insulin secretion. Potassium-dependent ATP channels at pancreatic beta cells open or close in response to blood glucose levels; this is the primary mechanism by which insulin release is regulated. 

High blood glucose levels lead to the closure of these channels, triggering insulin secretion, while low levels keep the channels open, preventing unnecessary insulin release.

In the heart, loss-of-function mutations are associated with the development of pulmonary arterial hypertension due to decreased functionality of potassium-dependent ATP channels, although function can be recovered pharmacologically.  [2.]

The gene for the ABCC8 protein may contain alterations or mutations that cause loss of function of the enzymes and can confer increased risk of disease in affected humans.  Testing for genetic alterations in the form of SNPs is increasingly available and can shed light on an individual’s potential for health and disease.  

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.

Function of ABCC8

The ABCC8 gene encodes the protein that affects potassium-dependent ATP (KATP) channel function, which has multiple downstream effects.  One prominent effect is increased or decreased insulin secretion by the beta cells of the pancreas.  

Mutations can cause both gain-of-function or loss-of-function, effectively increasing or decreasing SUR1 protein function and its downstream effects.

The Role of ABCC8 and Diabetes  [3., 4., 5.]

The KATP channel, influenced by the ABCC8 gene, is fundamental in maintaining glucose homeostasis within the body. In pancreatic beta cells, the opening and closing of this channel are key in the control of insulin release.

Mutations in the ABCC8 gene can lead to various dysfunctions in insulin secretion.

Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes with a prevalence ranging from 1 to 5%. There are at least 14 known MODY variations, of which mutations in the ABCC8 gene are one.  

In MODY 12, the ABCC8-dependent version of MODY, decreased function of the SUR affects the KATP channel which causes defective insulin secretion.  These patients typically respond well to sulfonylureas.  

Variants in ABCC8 can also result in hyperinsulinemic hypoglycemia (HH) due to impaired channel response and increased insulin secretion.

Congenital hyperinsulinism (CHI) is one manifestation of hyperinsulinemic hypoglycemia. 

CHI encompasses a range of rare β-cell disorders characterized by dysregulated insulin secretion, of which mutations in the ABCC8 gene are one.  CHI leads to recurrent episodes of hyperinsulinemic hypoglycemia which can result in seizures, developmental delay, and permanent brain damage if left untreated.  [KUMAR>>>>

Timely diagnosis and management are crucial to minimize the risk of neurocognitive impairment.

Alternatively, another mutation in the ABCC8 gene can cause permanent neonatal diabetes mellitus, characterized by low insulin secretion and hyperglycemia within the first 6 months of life.  [De LEON}

The Role of ABCC8 in Cardiac Health and Disease [2.] 

ABCC8's role extends to cardiac tissue as well, where it contributes to the heart's response to metabolic stress. 

In heart cells, the KATP channels help regulate cardiac contractility and protect the heart during ischemic events, where the heart muscle is deprived of oxygen.

Alterations in ABCC8 have been associated with pulmonary hypertension.  [2.] 

all quality of life for patients.

Lab Testing for ABCC8

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.

Order Genetic Testing

Click here to compare genetic test panels and order genetic testing for health-related SNPs.