4G/5G genetic polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with a risk of coronary artery disease, but only in younger people

Krzysztof Chizynski¹, Tadeusz Pietrucha²

Summary
Objective: Suppression of fibrinolysis by high circulating levels of plasminogen activator inhibitor-1 (PAI-1) may contribute to an increased risk of coronary disease. The PAI-1 gene, which contains nine exons and eight introns distributed over approximately 12.3 kb of DNA, has been localised to 7q21.3-22 of chromosome 7. The highest PAI-1 levels have been observed in 4G/4G homozygous individuals, and in this group an increased risk of CAD has been expected. In this paper, we present evidence for the association of the PAI-1 promoter genotype with CAD, and the contribution of PAI-1 4G/5G polymorphism in young and elderly CAD patients.
Material and methods: The study group included 514 patients (aged 31 to 86 yrs.; mean 55 yrs.), with angiographically-concerned CAD. The control group was 67 patients (aged 26 to 76 yrs.; mean 52 yrs.), without CAD (normal coronary arteries in angiography). Genotypes were determined by a polymerase chain reaction amplification of the genome DNA using the following allele specific primers: 5´-GTC TGG ACA CGT GGG GG-3´ for the insertion allele (5G) and 5´-GTC TGG ACA CGT GGG GA-3´ for the deletion allele (4G).
Results: PAI-1 promoter 4G5G polymorphism was related to the presence of CAD with an increased frequency of the 4G/4G genotype (p = 0.018), and decreased frequency of the 5G/5G genotype (p <0.0001), in subjects with coronary disease. The CAD odds ratio in subjects with the 4G/4G genotype was 2.08 (1.13-3.80) (p = 0.018) and in the subjects with 4G allele genotype (4G/5G and 4G/5G) was 2.84 (1.70-4.73) (p <0.0001). An additional analysis was performed on 121 elderly patients (over 65 yrs.), (111 subjects with and 10 without CAD) and in 460 younger ones (below 65 yrs.) (403 subjects with, and 57 without CAD). In elderly subjects there was no difference in the distribution of genotypes (4G+, 4G-) and alleles (4G, 5G). In elderly subjects with the 4G+ genotype there was no increased risk of CAD. In younger subjects with CAD, a higher frequency of the 4G+ genotypes (78.4% vs. 54.4%; p <0.0001) and 4G alleles (57.1% vs. 37.7%; p <0.0001) was observed. The odds ratio for having CAD was 3.05 (1.72-5.40) (p <0.0001) in the younger subjects with 4G+ genotype, and 2.20 (1.47-3.29) (p <0.0001) in the younger subjects with 4G allele.
Conclusion: Plasminogen activator inhibitor-1 promoter 4G/5G genotype is a risk factor for coronary disease in a Polish population, but only in younger people.

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