SCIENTIFIC BACKGROUND

APOA1

SCIENTIFIC BACKGROUND

Apo A-I is a crucial apoprotein involved in HDL metabolism. Primary Apo A-I deficiency is a rare autosomal recessive inherited metabolic defect characterized by extremely low serum concentrations of HDL (high-density lipoprotein) cholesterol (< 10 mg/dl) and Apo A-I (< 20 mg/dl). Multiple epidemiological studies have shown that lowered HDL-C concentrations, especially in combination with elevated LDL (low-density lipoprotein) cholesterol (LDL/HDL ratio >3.5), pose a risk for coronary heart disease. Apo A-I-deficient individuals generally have an increased coronary risk, caused by impaired efflux of cholesterol from peripheral cells. Variable phenotypic expression of planar xanthomas and corneal opacities are also characteristic of apo A-I deficiency. Pathogenic variants in the APOA1 gene (e.g., Apo A-I-Milano) have been described in some very rare cases. Despite moderately decreased HDL-C and Apo A-I in serum, these variants do not seem to cause an increased vascular risk but may even lead to a longer life expectancy due to accelerated HDL metabolism.

 

The APOA1 gene is located on chromosome 11q23 in the so-called apoprotein gene cluster, which also includes apoproteins C-III and A-IV. Transcription of these genes is partially regulated by common regulatory elements. In rare cases, combined defects of Apo A-I, C-III and A-IV have been described. In addition to Apo A-I deficiency, variants in the LCAT (LCAT deficiency, Fish Eye Disease) or ABCA1 (Tangier Disease) genes may be causative for HDL deficiency (hypoalphalipoproteinemia). The coronary risk is lower in LCAT deficiency and Tangier disease as compared to Apo A-I deficiency.

 

References

Geller et al. 2018, J Lipid Res. 59:2421 / Dron et al. 2017, J Lipid Res. 58:2162 / Lee et al. 2013, J Clin Lipidol 7:169 / Schaefer et al. 2010, Curr Opin Lipidol 21:289 / Tall et al., in Scriver et al. 2001: The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Chapter 121

GENES

APOA1
How to order

LATEST ARTICLES

Every year on April 25th, DNA Day celebrates the discovery of DNA’s double helix and the advances we’ve made in understanding genetics. D...

Read more

Neurodevelopmental disorders (NDDs) have diverse genetic origins, making diagnosis challenging. A new study analyzing over 1,100 pediatric patients f...

Read more

Colorectal cancer (CRC) remains one of the most prevalent and deadly cancers worldwide, with a significant number of cases presenting at an advanced ...

Read more

Carrier screening is a genetic test designed to identify whether an individual carries a gene with changes (mutations) associated with inherited diso...

Read more

Trisomy 13, also known as Patau syndrome, is a genetic condition in which cells in the body have three copies of chromosome 13 instead of two. The co...

Read more

The human brain develops through a complex series of events, with genes carefully regulating the formation of neurons and glial cells. A recent study...

Read more

Rare diseases affect between 300 and 400 million people worldwide – more than cancer and AIDS combined [1, 2], but despite this, many people face a...

Read more

Rosalind Elsie Franklin was a brilliant and meticulous research scientist whose interdisciplinary work made fundamental contributions to various area...

Read more

February, designated as Cancer Awareness Month, marks a time to reflect on the remarkable progress made in cancer research and to inspire hope for th...

Read more

Introduction Cardiovascular disease (CVD) is a major health issue as it remains a leading cause of death worldwide [1]. CVD is responsible for mor...

Read more