Determinants of plasma platelet-activating factor acetylhydrolase: heritability and relationship to plasma lipoproteins.
Plasma platelet-activating factor acetylhydrolase (PAF-AH) is the enzyme that inactivates PAF (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine). We determined the relative contributions of genetic and environmental factors to variation in plasma PAF-AH activity in 240 individuals from 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 correlated, indicating that familial aggregation of PAF-AH activity is due to genetic rather than to environmental factors. Among normolipidemic 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, plasma PAF-AH activity was measured in families with well-defined, monogenic disorders of LDL metabolism. Plasma PAF-AH activity cosegregated with plasma LDL-C concentrations in familial hypercholesterolemia, but not in familial hypobetalipoproteinemia. We speculate that the rate of removal of LDL from the circulation may determine the clearance rate of PAF-AH, thereby modulating the activity of PAF-AH in blood.
Guerra
R
R
Department of Statistical Science, Southern Methodist University, Dallas, TX 75275, USA.
Zhao
B
B
Mooser
V
V
Stafforini
D
D
Johnston
J M
JM
Cohen
J C
JC
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000367:Age Factors; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000235:genetics; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics; D006953:Hyperlipoproteinemia Type IV / Q000097:blood / Q000235:genetics; D006995:Hypobetalipoproteinemias / Q000097:blood / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D010375:Pedigree; D010741:Phospholipases A / Q000097:blood* / Q000235:genetics; D012044:Regression Analysis; D012737:Sex Factors
D008078:Cholesterol, LDL; D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008148:Lovastatin; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase