A Mutation in Plasma Platelet-activating Factor Acetylhydrolase (Val279Phe) Is a Genetic Risk Factor for Cerebral Hemorrhage but not for Hypertension

Hidemi Yoshida; Tadaatsu Imaizumi; Koji Fujimoto; Hiroyuki Itaya; Makoto Hiramoto; Nobuhiro Yoshimizu; Kazue Fukushi; Kei Satoh

doi:10.1055/s-0037-1615214

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 80(03): 372-375
DOI: 10.1055/s-0037-1615214

Rapid Communications

Schattauer GmbH

A Mutation in Plasma Platelet-activating Factor Acetylhydrolase (Val279Phe) Is a Genetic Risk Factor for Cerebral Hemorrhage but not for Hypertension

Hidemi Yoshida

¹From the Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki University School of Medicine, Hirosaki

,

Tadaatsu Imaizumi

¹From the Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki University School of Medicine, Hirosaki

,

Koji Fujimoto

¹From the Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki University School of Medicine, Hirosaki

,

Hiroyuki Itaya

¹From the Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki University School of Medicine, Hirosaki

,

Makoto Hiramoto

²From the Department of Neurosurgery, Yokohama General Hospital, Yokohama

,

Nobuhiro Yoshimizu

²From the Department of Neurosurgery, Yokohama General Hospital, Yokohama

,

Kazue Fukushi

³From the Aomori Health Control Center, Aomori, Japan

,

Kei Satoh

¹From the Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki University School of Medicine, Hirosaki

› Author Affiliations

Abstract

Summary

Platelet-activating factor (PAF) acetylhydrolase is an enzyme that inactivates PAF. Deficiency of this enzyme is caused by a missense mutation in the gene. We previously found a higher prevalence of this mutation in patients with ischemic stroke. This fact suggests that the mutation might enhance the risk for stroke through its association with hypertension. We have addressed this hypothesis by analyzing the prevalence of the mutation in hypertension. We studied 138 patients with essential hypertension, 99 patients with brain hemorrhage, and 270 healthy controls. Genomic DNA was analyzed for the mutant allele by the polymerase-chain reaction. The prevalence of the mutation was 29.3% (27.4% heterozygotes and 1.9% homozygotes) in controls and 36.2% in hypertensives and the difference was not significant. The prevalence in patients with brain hemorrhage was significantly higher than the control: 32.6% heterozygotes and 6.1% homozygotes (p <0.05). PAF acetylhydrolase deficiency may be a genetic risk factor for vascular diseases.

Full Text

References

References
1 Menotti A, Keys A, Blackburn H, Aravanis C, Dontas A, Fidanza F, Giam-paoli S, Karvonen M, Kromhout D, Nedeljkovic S, Nissinen A, Pekkanen J, Punsar S, Seccareccia F, Toshima H. Twenty-year stroke mortality and prediction in twelve cohorts of the seven countries study. Int J Epidemiol 1990; 19: 309-15.
2 Muirhead EE. Antihypertensive functions of the kidney. Hypertension 1980; 2: 444-64.
3 Blank ML, Lee TC, Fitzgerald V, Snyder F. A specific acetylhydrolase for 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (a hypotensive and platelet-activating lipid). J Biol Chem 1981; 256: 175-8.
4 Satoh K, Imaizumi T, Kawamura Y, Yoshida H, Takamatsu S, Mizuno S, Shoji B, Takamatsu M. Increased activity of the platelet-activating factor acetylhydrolase in plasma low density lipoprotein from patients with essential hypertension. Prostaglandins 1989; 37: 673-82.
5 Hofmann B, Rühling K, Spangeberg P, Ostermann G. Enhanced degradation of platelet-activating factor in serum from diabetic patients. Haemostasis 1989; 19: 180-4.
6 Satoh K, Yoshida Imaizumi T, Takamatsu S, Mizuno S. Platelet-activating factor acetylhydrolase in plasma lipoproteins from patients with ischemic stroke. Stroke 1992; 23: 1090-2.
7 Ostermann G, Lang A, Holz H, Rühling K, Winkler L, Till U. The degradation of platelet-activating factor in serum and its discriminative value in atherosclerotic patients. Thromb Res 1988; 52: 529-40.
8 Satoh K, Imaizumi T, Kawamura Y, Yoshida H, Hiramoto M, Takamatsu S, Takamatsu M. Platelet-activating factor (PAF) stimulates the production of PAF acetylhydrolase by the human hepatoma cell line, HepG2. J Clin Invest 1991; 87: 476-81.
9 Miwa M, Miyake T, Yamanaka T, Sugatani J, Suzuki Y, Sakata S, Araki Y, Matsumoto M. Characterization of serum platelet-activating factor (PAF) acetylhydrolase: correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children. J Clin Invest 1988; 82: 1983-91.
10 Tetta C, Bussolino F, Modena V, Montrucchio G, Segoloni G, Pescarmona G, Camussi G. Release of platelet-activating factor in systemic lupus erythematosus. Int Arch Allergy Appl Immunol 1990; 91: 244-56.
11 Stephens CJ, Graham RM, Sturm MJ, Richardson M, Taylor RR. Variation in plasma platelet-activating factor degradation and serum lipids after acute myocardial infarction. Coron Artery Dis 1993; 4: 187-93.
12 Graham RM, Stephens CJ, Silvester W, Leong LL, Sturm MJ, Taylor RR. Plasma degradation of platelet-activating factor in severely ill patients with clinical sepsis. Crit Care Med 1994; 22: 204-12.
13 Tjoelker LW, Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, Hooper S, Trong HL, Cousens LS, Zimmerman GA, Yamada Y, McIntyre TM, Prescott SM, Gray PW. Anti-inflammatory properties of a platelet-activating factor acetylhydrolase. Nature 1995; 374: 549-52.
14 Stafforini DM, Satoh K, Atkinson DL, Tjoelker LW, Eberhardt C, Yoshida H, Imaizumi T, Takamatsu S, Zimmerman GA, McIntyre TM, Gray PW, Prescott SM. Platelet-activating factor acetylhydrolase deficiency: a mis-sense mutation near the active site of an anti-inflammatory phospholipase. J Clin Invest 1996; 97: 2784-91.
15 Yoshida H, Satoh K, Koyama M, Hiramoto M, Takamatsu S. Deficiency of plasma platelet-activating factor acetylhydrolase: roles of blood cells. Am J Hematol 1996; 53: 158-64.
16 Hiramoto M, Yoshida H, Imaizumi T, Yoshimizu N, Satoh K. A mutation in plasma platelet-activating factor acetylhydrolase (Val279Phe) is a genetic risk factor for stroke. Stroke, 1997; 28: 2417-20.
17 Stafforini DM, Prescott SM, McIntyre TM. Human plasma platelet-activating factor acetylhydrolase. Purification and properties. J Biol Chem 1987; 262: 4223-30.
18 Venable ME, Zimmerman GA, McIntyre TM, Prescott SM. Platelet-activating factor: a phospholipid autacoid with diverse actions. J Lipid Res 1993; 34: 691-702.
19 Imaizumi T, Stafforini DM, Yamada Y, McIntyre TM, Prescott SM, Zimmerman GA. Platelet-activating factor: a mediator for clinicians. J Intern Med 1995; 238: 5-20.
20 Caramero C, Fernandez-Gallardo SD, Marin-Cao D, Inarrea JC, Santos JC, Lopez-Novoa J, Sanchez-Crespo M. Presence of platelet-activating factor in blood from humans and experimental animals. Its absence in anephric individuals. Biochem Biophys Res Commun 1984; 120: 789-96.
21 Maki N, Magness RR, Miyaura S, Gant NF, Johnston JM. Platelet-activating factor acetylhydrolase activity in normotensive and hypertensive pregnancies. Am J Obst Gynecol 1993; 168: 50-4.
22 Prescott SM, Zimmerman GA, McIntyre TM. Human endothelial cells in culture produce platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) when stimulated with thrombin. Proc Natl Acad Sci USA 1984; 81: 3534-8.
23 Zimmerman GA, McIntyre TM, Mehra M, Prescott SM. Endothelial cell-associated platelet-activating factor: a novel mechanism for signaling intercellular adhesion. J Cell Biol 1990; 110: 529-40.
24 Kubes P, Suzuki M, Granger DN. Modulation of PAF-induced leukocyte adherence and increased microvascular permeability. Am J Physiol 1990; 259: G859-64.
25 Kamitani T, Katamoto M, Tatsumi M, Katsuta K, Ono T, Kikuchi H, Kumada S. Mechanism(s) of the hypotensive effect of synthetic 1-O-octadecyl-2-O-acetyl-glycerol-3-phosphorylcholine. Eur J Pharmacol 1984; 98: 357-66.
26 Piper PJ, Stewart AG. Coronary vasoconstriction in the rat isolated perfused heart induced by platelet-activating factor is mediated by leukotriene C4. Br J Pharmacol 1986; 88: 595-605.
27 Kawaguchi H, Yasuda H. Effects of platelet-activating factor on conversion of angiotensin I to II. FEBS Lett 1987; 221: 305-8.
28 Cambien F, Poirier O, Lecerf L, Evans A, Combou JP, Arveiler D, Luc G, Bard JM, Bara L, Ricard S, Tiret L, Amouyel P, Alhenc-Gelas F, Soubrier F. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992; 359: 641-4.
29 Stremler KE, Stafforini DM, Prescott SM, Zimmerman GA, McIntyre TM. An oxidized derivative of phosphatidylcholine is a substrate for the platelet-activating factor acetylhydrolase from human plasma. J Biol Chem 1989; 264: 5331-4.