Human Apolipoprotein A-I Deficiency

Abstract

Our purpose is to review the characteristics of probands described with familial apolipoprotein (apo) A-I deficiency. Decreased plasma high density lipoprotein (HDL) cholesterol levels (<40 mg/dl in men and <50 mg/dl in women) have been associated with an increased risk of coronary heart disease (CHD) [1]. Marked HDL deficiency states (HDL cholesterol <5 mg/dl) and undetectable plasma apolipoprotein (apo) A-I levels have been reported in humans due to mutations at the AI/CIII/AIV gene locus [2–27]. These patients have a lack of apoA-I-containing HDL in plasma, normal or decreased triglyceride levels, normal low density lipoprotein (LDL) cholesterol levels, and often strikingly premature CHD [2–27]. In this regard, they differ from patients with homozygous Tangier disease, due to mutations in the ATP binding cassette A1 gene, who have detectable plasma apoA-I levels in preβ-1 HDL, defective cellular cholesterol efflux, hypertriglyceridemia, and decreased LDL cholesterol [28–30]. They also differ from patients with homozygous lecithin:cholesterol acyltransferase (LCAT) deficiency who have plasma apoA-I levels in the 10–20 mg/dl range found in both preβ-1 HDL and α-4 HDL, elevations of both plasma cholesterol and triglycerides, increased plasma free cholesterol, low density lipoprotein of abnormal electrophoretic mobility, and marked corneal opacification [31].