Freiberg Jacob J, Tybjaerg-Hansen Anne, Sillesen Henrik, Jensen Gorm B, Nordestgaard Børge G
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
Arterioscler Thromb Vasc Biol. 2008 May;28(5):990-6. doi: 10.1161/ATVBAHA.107.158873. Epub 2008 Feb 14.
Cysteinyl 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.
半胱氨酰白三烯参与炎症反应，可能还与早期颈动脉粥样硬化有关。我们检验了白三烯C4合成酶的-444 A/C和-1072 G/A多态性与缺血性脑血管病风险相关的假设。
我们对来自丹麦普通人群（哥本哈根城市心脏研究）的10592名个体进行了基因分型。在24年的随访期间，557人发生了缺血性脑血管病。-1072 A等位基因频率为0.07，-444 C为0.29。-1072 AA基因型的缺血性脑血管病累积发病率高于GG基因型（对数秩检验：P=0.002），-444 CC基因型低于AA基因型（对数秩检验：P=0.008）。联合基因型显示出相应的累积发病率差异（对数秩检验：P=0.003）。缺血性脑血管病的多因素校正风险比，-1072 AA基因型与GG基因型相比为2.8（1.4至5.7），-444 CC基因型与AA基因型相比为0.6（0.4至0.9），联合AA-AA基因型与GG-AA基因型相比为2.5（1.2至5.4），联合GG-CC基因型与GG-AA基因型相比为0.6（0.4至0.9）。基因型与深静脉血栓形成风险、严重颈动脉粥样硬化或血小板及凝血因子水平无关。
白三烯C4合成酶-1072 AA基因型预示缺血性脑血管病风险增加，而-444 CC基因型预示风险降低。
