4. Plasminogen Activator Inhibitor-1 (PAI-1)
PAI-1 is used to evaluate the risk of thrombosis. It is a serine protease inhibitor (serpin), therefore it is also known as serpin E1. Human SERPINE1 gene encodes for PAI-1. PAI-1 inhibits Fibrinolysis through the inhibition of the serine proteases, Tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), which activate plasminogen. So any increase in PAI-1 decreases fibrinolysis consequently increasing the risk of thrombosis.
PAI-1 gene (SERPINE1 gene) is found on chromosome 7q21.3-q22. Its wild type promoter contains five consecutive G residues while the mutant promoter contains only four consecutive G residues resulting in an increase in PAI-1. There are three genotypes: …show more content…
There are two allelic polymorphisms (A1 and A2). Premature myocardial infarction, unstable angina and coronary stent thrombosis are associated with A2. There are three genotypes: normal (A1/A1), heterozygous (A1/A2) and homozygous (A2/A2).
Caucasian population
A1/A1 64%
A1/A2 34%
A2/A2 2%
Homozygous wild-type (A1/A1) Normal
Heterozygous (A1/A2) Slightly increased risk of thrombosis
Homozygous mutant (A2/A2) Significantly increased risk of thrombosis
C. Risk of Coronary Artery Disease (CAD)
1. Endothelial Nitric Oxide Synthase (eNOS)
eNOS is used to identify risk of developing CAD. One of the factors that maintain vascular tone is nitric oxide, which is synthesized through eNOS. Deficiency in eNOS causes a deficiency in nitric oxide, which may cause coronary spasm, angina pectoris or myocardial infarction.
eNOS gene is found on chromosome 7q36. Mutations in the eNOS gene (T-786C) decrease the nitric oxide synthesis thus increasing the risk of CAD. There are three genotypes: normal (-/-), heterozygous (+/- for T-786C) and homozygous (+/+ for T-786C). T-786C mutation is very …show more content…
Stromelysin-1
Stromelysin-1 is used to identify risk of developing CAD. Stromelysin-1 or matrix metalloproteinase-3 (MMP-3) is a matrix remodeling enzyme which degrades collagen, proteoglycans, gelatin and elastin. Therefore MMP-3 affects the matrix composition, which affects lipid accumulation, vascular remodeling and plaque instability resulting in cardiovascular disease.
Human MMP-3 gene is found on chromosome 11q22.3. The wild type promoter contains 5 consecutive A residues (5A allele) while the mutant contains 6 consecutive A residues (6A allele), resulting in a decrease in the stromelysin-1 levels. Any decrease in stromelysin-1 levels decreases proteolytic activity, increases extracellular matrix deposition thus causing artherosclerosis. There are three genotypes: normal (5A/5A), heterozygous (5A/6A) and homozygous (6A/6A).
Normal (5A/5A) Normal stromelysin-1 levels
Heterozygous (5A/6A) • Reduced stromelysin-1 levels
• Increased risk for CAD
Homozygous (6A/6A) • Reduced stromelysin-1
PAI-1 is used to evaluate the risk of thrombosis. It is a serine protease inhibitor (serpin), therefore it is also known as serpin E1. Human SERPINE1 gene encodes for PAI-1. PAI-1 inhibits Fibrinolysis through the inhibition of the serine proteases, Tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), which activate plasminogen. So any increase in PAI-1 decreases fibrinolysis consequently increasing the risk of thrombosis.
PAI-1 gene (SERPINE1 gene) is found on chromosome 7q21.3-q22. Its wild type promoter contains five consecutive G residues while the mutant promoter contains only four consecutive G residues resulting in an increase in PAI-1. There are three genotypes: …show more content…
There are two allelic polymorphisms (A1 and A2). Premature myocardial infarction, unstable angina and coronary stent thrombosis are associated with A2. There are three genotypes: normal (A1/A1), heterozygous (A1/A2) and homozygous (A2/A2).
Caucasian population
A1/A1 64%
A1/A2 34%
A2/A2 2%
Homozygous wild-type (A1/A1) Normal
Heterozygous (A1/A2) Slightly increased risk of thrombosis
Homozygous mutant (A2/A2) Significantly increased risk of thrombosis
C. Risk of Coronary Artery Disease (CAD)
1. Endothelial Nitric Oxide Synthase (eNOS)
eNOS is used to identify risk of developing CAD. One of the factors that maintain vascular tone is nitric oxide, which is synthesized through eNOS. Deficiency in eNOS causes a deficiency in nitric oxide, which may cause coronary spasm, angina pectoris or myocardial infarction.
eNOS gene is found on chromosome 7q36. Mutations in the eNOS gene (T-786C) decrease the nitric oxide synthesis thus increasing the risk of CAD. There are three genotypes: normal (-/-), heterozygous (+/- for T-786C) and homozygous (+/+ for T-786C). T-786C mutation is very …show more content…
Stromelysin-1
Stromelysin-1 is used to identify risk of developing CAD. Stromelysin-1 or matrix metalloproteinase-3 (MMP-3) is a matrix remodeling enzyme which degrades collagen, proteoglycans, gelatin and elastin. Therefore MMP-3 affects the matrix composition, which affects lipid accumulation, vascular remodeling and plaque instability resulting in cardiovascular disease.
Human MMP-3 gene is found on chromosome 11q22.3. The wild type promoter contains 5 consecutive A residues (5A allele) while the mutant contains 6 consecutive A residues (6A allele), resulting in a decrease in the stromelysin-1 levels. Any decrease in stromelysin-1 levels decreases proteolytic activity, increases extracellular matrix deposition thus causing artherosclerosis. There are three genotypes: normal (5A/5A), heterozygous (5A/6A) and homozygous (6A/6A).
Normal (5A/5A) Normal stromelysin-1 levels
Heterozygous (5A/6A) • Reduced stromelysin-1 levels
• Increased risk for CAD
Homozygous (6A/6A) • Reduced stromelysin-1