Genetic Polymorphism of PAI-1 Gene and Cardiovascular Disease: eta-analysis of Case-Control Studies

BACKGROUND: Previous reports have suggested that alleles at the plasminogen activator inhibitor-1 (PAI-1) gene are associated with increased risk of developing coronary artery disease, including myocardial infarction and stroke through their effect on PAI-1 levels. Method: We attempted to search English literatures for all reports of possible effects of PAI-1 gene on cardiovascular disease in human published prior to November 1998. We used a Mantel-Haenszel method (fixed effect model) and random effect model, respectively, to perform a meta-analysis of 7 case-control studies that provided information related to the effects of PAI-1 gene on risk of cardiovascular disease. RESULTS: From 7 studies for diagnosed cardiovascular disease, the relative frequencies of the three genotypes among controls was (5G/5G) (homozygous normal), 24.5%; (4G/5G) (heterozygous), 48.2%, and (4G/4G) (homozygous for the mutant, 675 GGGG), 27.3%. These relative frequencies in cases were 21.7% for 5G/5G, 48.0% for 4G/5G, and 30.3% for 4G/4G. In fixed effect model, compared with those with genotype (5G/5G), the overall odds ratio (OR) for cardiovascular disease among those with (4G/5G) was 1.12 (95% CI, 0.93 to 1.34), and it was 1.20 (1.01 to 1.44) for the (4G/4G) genotype. For five studies with myocardial infarction as the outcome, the overall OR of myocardial infarction was 1.20 (0.99 to 1.47) for those with (4G/5G) and 1.24 (1.00, 1.54) for those with (4G/4G) genotypes, respectively. CONCLUSION: Our findings provide support for the weak association between PAI-1 gene and cardiovascular disease, in particular, myocardial infarction.

Plasma Levels of Fibrinogen as a Risk Factor for Coronary Artery Disease / 대한임상병리학회지

BACKGROUND: Fibrinogen is an essential cofactor for blood coagulation. The fibrinogen level has been identified as a risk factor for coronary artery disease(CAD) and stroke, but the relationship between plasma fibrinogen levels and number of atherosclerotic vesssels has been less investigated. The aim of this study is assess the possible association between plasma fibrinogen levels and the number of coronary stenosis in patients with CAD undergoing coronary catheterization. We also investigated the usefulness of plasma fibrinogen to predict CAD in a case-control study of the middle-aged men and women. METHODS: We measured plasma fibrinogen, total cholesterol, HDL-cholesterol and triglyceride in 121 patients with CAD and in 109 healthy controls. Multivariate logistic regression models were performed to assess risk factors for CAD. RESULTS: Plasma fibrinogen levels were significantly elevated in CAD group vs control group, 413.9+/-119.4 vs 296.3+/-74.1 mg/dL(P<0.001), respectively. The levels of plasma fibrinogen were not different according to the number of coronary stenosis. Multivariate logistic regression analysis of fibrinogen level and risk factors revealed 3 independent predictors of CAD: fibrinogen, body mass index and diabetes mellitus. Those with fibrinogen levels of 331-420 mg/dL had a 6.36-fold increased risk than fibrinogen levels of less than 270 mg/dL, while fibrinogen levels higher than 420 mg/dL had 3.53-fold increased risk. CONCLUSIONS: These results provide the evidence that plasma fibrinogen is associated with an increased risk of CAD. However, the plasma fibrinogen was not correlated with the severity of coronary stenosis.

A Study of Major Gene Dominant Family for Factor VII Concentration: Segregation Analysis / 한국역학회지

Elevated plasma level of factor VII is a risk factor for coronary artery disease. We investigated environmental, familial, and genetic influences on factor VII levels. We used maximum likelihood segregation analysis to fit several genetic and nongenetic modes of inheritance to the data to determine whether Mendelian inheritance of a major gene could best explain the familial distribution of factor VII. The study population included 414 family members of 67 subjects who had undergone elective coronary arteriography. The factor VII level was adjusted for age, gender, body mass index, smoking and alcohol drinking (R2=20.6%). Factor VII levels revealed strong familial aggregation with estimated correlation spouse of 0.12, parent-offspring of 0.31, and siblings of 0.40. Regressive models were used to examine inter-individual variation in adjusted factor VII levels in these 67 families. This analysis strongly favored a major gene model with codominant transmission. Genotypic means were 111.6, 123.2, and 184.3% with relative frequencies of 59.4%, 35.4%, and 5.2%. This putative major gene explains 39.9% of the total variance of factor VII. Likelihood was used to search for etiologic heterogeneity by sorting pedigrees into groups that favor one model over another. Compared to pedigrees less favoring Mendelian models, pedigrees favoring Mendelian codominant models have almost 8 times earlier onset of coronary heart disease. These family data suggest that there are strong familial and genetic effects on the factor VII activity in these high risk families. Therefore, linkage studies in these families may be worthwhile to clarify the molecular basis of factor VII levels.