TY - JOUR
T1 - Determinants of plasma platelet-activating factor acetylhydrolase
T2 - Heritability and relationship to plasma lipoproteins
AU - Guerra, Rudy
AU - Zhao, Biren
AU - Mooser, Vincent
AU - Stafforini, Diana
AU - Johnston, John M.
AU - Cohen, Jonathan C.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1997/11
Y1 - 1997/11
N2 - 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, hereby modulating the activity of PAF-AH in blood.
AB - 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, hereby modulating the activity of PAF-AH in blood.
KW - Familial hypercholesterolemia
KW - Familial hypobetalipoproteinemia
KW - Lovastatin
KW - Low density lipoprotein
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M3 - Article
C2 - 9392426
AN - SCOPUS:0030699106
SN - 0022-2275
VL - 38
SP - 2281
EP - 2288
JO - Journal of lipid research
JF - Journal of lipid research
IS - 11
ER -