DETERMINANTS OF PLASMA PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE - HERITABILITY AND RELATIONSHIP TO PLASMA-LIPOPROTEINS

Plasma platelet-activating factor acetylhydrolase (PAF-AH) is the enzy me that inactivates PAF (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) . We determined the relative contributions of genetic and environmenta l factors to variation in plasma PAF-AH activity in 240 individuals fi om 60 nuclear families. Regression of mean-offspring PAF-AH activity on the mid-parent value indicated that 62% of the variation in plasma PAF-AH activity was heritable. Spousal values were weakly negatively c orrelated, indicating thar familial aggregation of PAF-AH activity is due to genetic rather :bar, to environmental factors. Among normolipid emic individuals, plasma PAF-AH activity was strongly correlated with the plasma concentration of low density lipoprotein cholesterol (LDL-C ), and treatment with lovastatin resulted in proportional decreases in plasma PAF-AH activity and LDL-C concentrations. To further elucidate the relationship between PAF-AH and plasma concentrations of LDL, pla sma PAF-AH activity was measured in families with well-defined, monoge nic disorders of LDL metabolism Plasma PAF-AH activity cosegregated wi th plasma LDL-C concentrations in familial hypercholesterolemia, but n ot in familial hypobetalipoproteinemia. We speculate that the rate of removal of LDL from the circulation may determine the clearance rate o f PAF-AH, thereby modulating the activity of PAF-AH in blood.