EVIDENCE AGAINST ALTERATIONS IN LECITHIN-CHOLESTEROL ACYLTRANSFERASE (LCAT) ACTIVITY IN FAMILIAL COMBINED HYPERLIPIDEMIA

Elevated concentrations of plasma cholesterol and triglycerides are ch aracteristic of familial combined hyperlipidemia (FCHL) which may also present with reduced high density lipoprotein (HDL) cholesterol conce ntrations. Lecithin:cholesterol acyltransferase (LCAT) plays a key rol e in reverse cholesterol transport by converting unesterified choleste rol to cholesterol ester in the process of maturation of HDL in the pr esence of its activator, apolipoprotein (apo) A-I. We hypothesised tha t alterations in LCAT activity or plasma concentrations or gene sequen ce of apo A-I could influence HDL metabolism in these patients. We stu died cholesterol concentrations of high density lipoprotein subfractio ns and LCAT activity in 25 FCHL subjects and 48 controls. Total HDL (p = 0.018) and HDL2 (p = 0.008) were significantly decreased in the FCH L group compared with controls. After analyses with adjusted data only HDL2 remained significantly decreased in the FCHL group (p = 0.050). The LDLc/HDLc and A-I/HDLc ratios were significantly elevated in the F CHL group (p < 0.0001), the latter suggesting the existence of composi tional differences in the HDL particles of the FCHL individuals. LCAT activity assessed in the FCHL (19.94 +/- 3.95 nmol/ml per h) and contr ol (20.13 +/- 6.86 nmol/ml per h) groups showed no statistically signi ficant differences. A significant positive correlation of LCAT activit y with total HDL (r = 0.42), HDL3 cholesterol (r = 0.46) and apolipopr otein A-I (r = 0.47) was observed in affected subjects but not in cont rols. An association between a G(-75)-A variation in the promoter regi on of the apo A-I gene and elevated concentrations of apo A-I (p = 0.0 09) and apo C-III (p = 0.041) was observed. This association was stron gly influenced by the status of the subject providing further evidence for a regulatory role of this genetic region in the expression of FCH L. Our data suggests that LCAT activity is normal in FCHL and, therefo re, does not account for the abnormalities observed in these patients essentially with regard to the HDL2 subfraction. (C) 1998 Elsevier Sci ence Ireland Ltd. All rights reserved.