Association of the 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor-1 with abdominal aortic aneurysms

被引:46
作者
Rossaak, JI [1 ]
van Rij, AM [1 ]
Jones, GT [1 ]
Harris, EL [1 ]
机构
[1] Univ Otago, Dunedin Sch Med, Dept Surg, Dunedin, New Zealand
关键词
D O I
10.1067/mva.2000.104589
中图分类号
R61 [外科手术学];
学科分类号
摘要
Purpose. A familial component has previously been identified in 11% to 20% of patients with abdominal aortic aneurysms (AAAs). The genetic basis of familial AAA remains elusive, however. Matrix metalloproteinases have been implicated in aneurysm development; and plasmin, a serine protease, activates metalloproteinases. Plasminogen activator inhibitor-1 (PAI-1) regulates plasmin activation through the tissue plasminogen activators. A polymorphism within the promoter area of PAI-I has been described that modifies PAI-1 expression and consequently plasminogen activation. The 4G homozygous variant is associated with increased PAI-1 expression and consequently reduced plasmin activity and therefore may be selected against in-familial AAA. The purpose of this study was to investigate the incidence of the 4G/5G insertion/deletion polymorphism in the promoter area of the PAI-1 gene in a population with AAA. Methods: Patients seen at a tertiary referral center for repair of abdominal aortic aneurysms were recruited. DNA was extracted from blood. Primers were designed to amplify a 99 (5G)-base pair (bp) and a 98 (4G)-bp fragment bracketing the polymorphism. The 5' primer was mutated to allow a restriction endonuclease to cleave the 5G polymorphism into a 77-bp and a 22-bp fragment. Samples were run on agarose gels and stained with ethidium bromide. Results: One hundred ninety patients with AAAs, including 39 patients with strong family histories and 163 controls were examined. The frequency of the 4G:5G alleles in the AAA population and in the control population was 0.6:0.4. However, 26% of patients with familial AAA were homozygous 5G compared with 13% of the control population. The 4G-allele frequency was 0.47 in the familial AAAs, compared with 0.62 in the nonfamilial patients (P=.02) and 0.61 in the control population (P=.03). Conclusion: The selection against the 4G4G genotype in the familial AAA population may indicate a role for PAT in the development of AAA in this population.
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页码:1026 / 1032
页数:7
相关论文
共 46 条
[21]   Prevalence of abdominal aortic aneurysms in men with diabetes [J].
Mattes, E ;
Davis, TME ;
Yang, DN ;
Ridley, D ;
Lund, H ;
Norman, PE .
MEDICAL JOURNAL OF AUSTRALIA, 1997, 166 (12) :630-633
[22]   A SIMPLE SALTING OUT PROCEDURE FOR EXTRACTING DNA FROM HUMAN NUCLEATED CELLS [J].
MILLER, SA ;
DYKES, DD ;
POLESKY, HF .
NUCLEIC ACIDS RESEARCH, 1988, 16 (03) :1215-1215
[23]  
Murphy G, 1992, Matrix Suppl, V1, P224
[24]   STEPWISE ACTIVATION MECHANISMS OF THE PRECURSOR OF MATRIX METALLOPROTEINASE-3 (STROMELYSIN) BY PROTEINASES AND (4-AMINOPHENYL)MERCURIC ACETATE [J].
NAGASE, H ;
ENGHILD, JJ ;
SUZUKI, K ;
SALVESEN, G .
BIOCHEMISTRY, 1990, 29 (24) :5783-5789
[25]   MATRIX METALLOPROTEINASES IN ABDOMINAL AORTIC-ANEURYSM - CHARACTERIZATION PURIFICATION, AND THEIR POSSIBLE SOURCES [J].
NEWMAN, KM ;
MALON, AM ;
SHIN, RD ;
SCHOLES, JV ;
RAMEY, WG ;
TILSON, MD .
CONNECTIVE TISSUE RESEARCH, 1994, 30 (04) :265-276
[26]   IDENTIFICATION OF MATRIX METALLOPROTEINASE-3 (STROMELYSIN-1) AND METALLOPRROTEINASE-9 (GELATINASE-B) IN ABDOMINAL AORTIC-ANEURYSM [J].
NEWMAN, KM ;
OGATA, Y ;
MALON, AM ;
IRIZARRY, E ;
GANDHI, RH ;
NAGASE, H ;
TILSON, MD .
ARTERIOSCLEROSIS AND THROMBOSIS, 1994, 14 (08) :1315-1320
[27]   Plasminogen activator inhibitor-1 promoter 4G/5G genotype and plasma levels in relation to a history of myocardial infarction in patients characterized by coronary angiography [J].
OsseiGerning, N ;
Mansfield, MW ;
Stickland, MH ;
Wilson, IJ ;
Grant, PJ .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1997, 17 (01) :33-37
[28]   DETERMINANTS OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 ACTIVITY IN TREATED NIDDM AND ITS RELATION TO A POLYMORPHISM IN THE PLASMINOGEN-ACTIVATOR INHIBITOR-1 GENE [J].
PANAHLOO, A ;
MOHAMEDALI, V ;
LANE, A ;
GREEN, F ;
HUMPHRIES, SE ;
YUDKIN, JS .
DIABETES, 1995, 44 (01) :37-42
[29]   Influence of risk factors on peripheral and cerebrovascular disease in men with coronary artery disease, low high-density lipoprotein, cholesterol levels, and desirable low-density lipoprotein cholesterol levels [J].
Papademetriou, V ;
Narayan, P ;
Rubins, H ;
Collins, D ;
Robins, S .
AMERICAN HEART JOURNAL, 1998, 136 (04) :734-740
[30]  
PEARCE WH, 1992, J VASC SURG, V16, P784