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ABC1: the gene for Tangier disease and beyond
1Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Insights
Mutations in the ATP-binding cassette transporter 1 gene (ABC1) cause Tangier disease, leading to very low high-density lipoprotein cholesterol (HDL-C). This discovery advances understanding of reverse cholesterol transport and may aid in assessing CHD genetic risk and developing new treatments.
Area of Science:
- Biochemistry
- Genetics
- Cardiovascular Medicine
Background:
- Coronary heart disease (CHD) is a leading cause of death, often associated with low high-density lipoprotein cholesterol (HDL-C).
- The mechanisms regulating plasma HDL-C levels and reverse cholesterol transport remain largely unknown.
- Low HDL-C is a common biochemical abnormality in CHD patients.
Purpose of the Study:
- To investigate the genetic basis of HDL-C regulation.
- To understand the role of the ATP-binding cassette transporter 1 gene (ABC1) in lipoprotein metabolism.
- To explore the implications of ABC1 mutations for CHD.
Main Methods:
- Genetic analysis of individuals with Tangier disease.
- Biochemical assessment of plasma lipid levels.
- Studies on lipoprotein metabolism and reverse cholesterol transport.
Main Results:
- Mutations in the ABC1 gene are responsible for Tangier disease.
- Tangier disease patients exhibit virtually absent circulating HDL.
- This finding links ABC1 to HDL metabolism and reverse cholesterol transport.
Conclusions:
- The ABC1 gene plays a critical role in maintaining plasma HDL-C levels.
- Understanding ABC1 function provides insights into lipoprotein metabolism.
- This knowledge may lead to improved CHD risk assessment and novel therapeutic strategies.
Abstract:
Coronary heart disease (CHD) is the leading cause of death in America. CHD is multifactorial, and low plasma high-density lipoprotein cholesterol (HDL-C) levels are among the most common biochemical abnormalities observed in CHD patients. The mechanisms controlling plasma HDL-C levels are poorly understood. However, several groups recently reported that mutations at the ATP-binding cassette transporter 1 gene (ABC1) are responsible for a rare disorder known as Tangier disease, which is characterized in the homozygous state by the virtual absence of circulating plasma HDL. This new finding represents a major breakthrough in our knowledge of lipoprotein metabolism and, more specifically, the reverse cholesterol transport. This information could lead to a more precise assessment of the genetic predisposition to CHD as well as to new therapeutic tools to prevent and treat CHD.