Nicholas Ossei-Gerning

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

To investigate the relationship between an insertion/deletion (4G/5G) polymorphism in the promoter region of the plasminogen activator inhibitor-1 (PAI-1) gene and the phenotypes of PAI-1 levels, coronary atheroma, and a past history of coronary thrombosis, we studied 453 patients (320 men and 133 women) characterized by coronary angiography. Patients were classified as having normal vessels (n = 125) or single-vessel (n = 92) or multivessel (n = 232) coronary disease on the basis of > or = 50% stenosis. PAI-1 antigen levels were highest in patients with the 4G/4G genotype (22.5 ng/mL), with a stepwise decrease in levels as the number of 4G alleles decreased (21.5 ng/mL for 4G/5G and 15.8 ng/mL for 5G/5G, P = .02) after adjusting for age, sex, triglyceride levels, and body mass index (BMI). The association between triglyceride level and PAI-1 was genotype specific, with a steeper slope in subjects with the 4G/4G genotype (P = .004). A gene-environment interaction between BMI, PAI-1, and genotype was observed, with a steeper association in patients with the 5G/5G genotype (P = .02). The 4G/4G genotype was significantly associated with a history of myocardial infarction (P < .03; odds ratio, 2.0; 95% CI, 1.1 to 3.7). This relationship was stronger in subjects with diseased vessels (P = .006). There was no relationship between either PAI-1 genotype or levels and the presence of atheroma. Our data suggest that PAI-1 promoter polymorphism influences the development of myocardial infarction through its effect on thrombus formation in patients with preexisting coronary atheroma.

The paraoxonase Gln-Arg 192 polymorphism in subjects with ischaemic heart disease.

BackgroundHuman serum paraoxonase activity is related to the paraoxonase Gln-Arg 192 polymorphism genotype. The purpose of this study was to investigate the association between the Gln-Arg 192 polymorphism of paraoxonase and ischaemic heart disease (IHD). MethodsFour hundred and forty patients with a history suggestive of IHD. and characterized by coronary angiography. and 527 healthy controls were studied. Patients were grouped according to paraoxonase genotype, presence or absence of diseased coronary arteries (on the basis of 50% stenosis), and history of myocardial infarction as judged by World Health Organization criteria. Patients were genotyped for the paraoxonase Gln-Arg 192 polymorphism by polymerase chain reaction. ResultsNo significant relationship was found between paraoxonase genotype and age, sex, body mass index, smoking. triglycerides or hypertension However, by one-way analysis of variance, cholesterol was found to be significantly associated with paraoxonase genotype in male patients [AA 5.9 (5.8–6.1), AB 6.2 (6.0–6.4), BB 5.7 (54–6.1); P= 0.04].The Gln-Arg 192 polymorphism was found to have no significant effect on the number of patients having diseased coronary arteries, or having myocardial infarction (P= 0.97 for both). In logistic regression models, paraoxonase genotype did not remain a significant independent predictor of stenosis or myocardial infarction. ConclusionThis study failed to show an association between the Gln-Arg 192 polymorphism of paraoxonase and the clinical phenotypes of coronary atheroma and acute myocardial infarction.

Angiotensin-converting enzyme (ACE) gene polymorphisms in patients characterised by coronary angiography

Abstract The angiotensin converting enzyme (ACE) gene is implicated as a risk factor for coronary artery disease and myocardial infarction (MI). An insertion/deletion (I/D) polymorphism is believed to be in linkage disequilibrium with a functional site elsewhere. Ten polymorphisms have recently been identified in the ACE gene. We screened patients undergoing coronary angiography (n = 258) for six of these polymorphisms (T-5491C, T-93C, A-240T, T1237C, D/I and 4656(CT)2/3), and identified a further two rare polymorphisms. ACE levels were associated with genotype for all polymorphisms analysed individually by one way ANOVA (P < 0.0005). The polymorphisms occurring in the 5′ region were in negative linkage disequilibrium with the exonic and 3′ region polymorphisms. The A-240T polymorphism had the greatest association with ACE levels (R2 = 14%); none of the others were significantly associated with levels when adjustment was made for A-240T. None of the polymorphisms were associated with the extent of coronary atheroma. Two of the promoter polymorphisms (A-240T and T-93C) were weakly related to the occurrence of MI (P = 0.03 and P = 0.05, respectively, by χ2 analysis). The TT genotype of A-240T appeared to be protective against MI with an odds ratio of 0.31 (95% confidence interval, 0.12, 0.83). These findings indicate that polymorphisms in the ACE gene promoter region may have a stronger association with disease than the I/D polymorphism.