Familial Apolipoprotein A-I, C-III and A-IV Deficiency

Abstract

Apolipoprotein (apo) A-I is the major protein of high density lipoproteins (HDL), while apoC-III and apoA-IV are minor protein components which are also found within triglyceride-rich lipoprotein particles (1). Decreased levels of plasma HDL cholesterol and apoA-I have been demonstrated to be risk factors for premature coronary artery disease (CAD) (2,3). The genes coding for apoA-I, apoC-III, and apoA-IV are adjacent to one another on the long arm of chromosome 11 (4). Restriction fragment length polymorphisms (RFLPs) within this region SstI site 3′ to the apoA-I gene, and SstI within the 31 untranslated region of the apoC-III gene) have been associated with premature coronary atherosclerosis, decreased HDL, and hypertriglyceridemia (5–8). A kindred has been described in which two sisters developed severe coronary atherosclerosis in their late twenties and were noted to have marked HDL deficiency and trace or undetectable levels of apoA-I and apoC-III in their plasma. They also had diffuse yellow-orange planar xanthomas, and mild corneal opacification (9). Obligate heterozygotes in this kindred had levels of HDL cholesterol, apoA-I and apoC-III which were approximately 50% of normal. This disorder, known as familial apolipoprotein A-I and C-III deficiency, has recently been shown to be due to a DNA rearrangement involving the adjacent apoA-I and apoC-III genes (10) (more detailed description of this disorder is presented by Dr. S.K. Karathanasis in another chapter of the present volume).