Jacob J Freiberg, Anne Tybjaerg-Hansen, Henrik Sillesen, Gorm B Jensen, Børge G Nordestgaard
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
Arteriosclerosis, thrombosis, and vascular biology 2008 MayCysteinyl leukotrienes are involved in inflammation and possibly in early carotid atherosclerosis. We tested the hypothesis that the -444 A/C and -1072 G/A polymorphisms of the leukotriene C(4) synthase associate with risk of ischemic cerebrovascular disease. We genotyped 10 592 individuals from the Danish general population, the Copenhagen City Heart Study. During 24 years of follow-up, 557 individuals developed ischemic cerebrovascular disease. The allele frequency was 0.07 for -1072 A and 0.29 for -444 C. Cumulative incidence for ischemic cerebrovascular disease was higher for -1072 AA versus GG genotype (log-rank: P=0.002), and lower for -444 CC versus AA genotype (log-rank: P=0.008). Combined genotypes showed corresponding cumulative incidence differences (log-rank: P=0.003). Multifactorially adjusted hazard ratios for ischemic cerebrovascular disease were 2.8(1.4 to 5.7) for -1072 AA versus GG genotype, 0.6(0.4 to 0.9) for -444 CC versus AA genotype, 2.5(1.2 to 5.4) for combined AA-AA versus GG-AA genotype, and 0.6(0.4 to 0.9) for combined GG-CC versus GG-AA genotype. Genotype did not associate with risk of deep venous thrombosis or severe carotid atherosclerosis, or with levels of platelets and coagulation factors. Leukotriene C(4) synthase -1072 AA genotype predict increased risk, whereas -444 CC genotype predict decreased risk of ischemic cerebrovascular disease.
Jacob J Freiberg, Anne Tybjaerg-Hansen, Henrik Sillesen, Gorm B Jensen, Børge G Nordestgaard. Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease. Arteriosclerosis, thrombosis, and vascular biology. 2008 May;28(5):990-6
PMID: 18276912
View Full Text