Abstract 2185: Novel Mutations in Leukotriene C4 Synthase and Risk of Ischemic Cardiovascular Disease
Rationale: Atherosclerotic diseases are inflammatory conditions where cysteinyl leukotrienes have been identified to play an important role. Furthermore, cysteinyl leukotrienes may also affect thrombi formation.
Objectives: We tested the hypothesis that new genetic variation likely to affect the function of leukotriene C4 synthase is associated with risk of venous thromboembolism, ischemic stroke, and myocardial infarction.
Findings: Resequencing of the gene coding for leukotriene C4 synthase in an extreme risk population with more than 1500 individuals revealed 17 new mutations, of which 4 potentially could change protein function. Based on more than 50,000 individuals, odds ratios for venous thromboembolism were 2.0(95% CI:1.3–3.2) for splice-site mutation IVS3+1G>A heterozygote vs. wildtype and 1.9(1.5–2.7) for any mutation heterozygote vs. wildtype (Figure⇓). Corresponding values were 2.0(1.3–3.2) and 1.5(1.1–2.1) for ischemic stroke, and 1.0(0.8 –1.3) and 1.2(1.0 –1.4) for myocardial infarction.
Conclusions: Four new mutations that potentially could change the function of leukotriene C4 synthase were associated with increased risk of venous thrombo-embolism, ischemic stroke, and myocardial infarction. Our findings indicate that leukotriene C4 synthase activity could be important in cardiovascular diseases.