Freiberg Jacob J, Dahl Morten, Tybjaerg-Hansen Anne, Grande Peer, Nordestgaard Børge G
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark.
J Mol Cell Cardiol. 2009 Apr;46(4):579-86. doi: 10.1016/j.yjmcc.2009.01.002.
Ischemic cardiovascular disease and obstructive pulmonary disease involve inflammation. Leukotrienes may be important pro-inflammatory mediators. We tested the hypothesis that the (-1072)G > A and (-444)A > C promoter polymorphisms of leukotriene C4 synthase confer risk of transient ischemic attack (TIA), ischemic stroke, ischemic heart disease (IHD), asthma, and chronic obstructive pulmonary disease (COPD). We genotyped individuals from the Danish general population, the Copenhagen City Heart Study, and Danish patients with IHD/coronary atherosclerosis, the Copenhagen Ischemic Heart Disease Study. We used prospective (n = 10,386), cross-sectional (n = 10,386), and case-control (n = 2392 + 5012) designs. Allele frequency was 0.07 for (-1072)A and 0.29 for (-444)C. Cumulative incidence for TIA was higher for (-1072)AA versus GG genotype (log-rank: p < 0.001), and lower for (-444)CC versus AA genotype (log-rank: p = 0.03). Cumulative incidence for ischemic stroke was also lower for (-444)CC versus AA genotype (log-rank: p = 0.04). Multifactorially adjusted hazard ratios for TIA were 5.2(95% CI:1.9-14) for (-1072)AA versus GG genotype, and 0.4(0.2-1.0) for (-444)CC versus AA genotype. Corresponding values were 1.9 (0.7-5.2) and 0.7 (0.5-1.0) for ischemic stroke, and 0.8 (0.4-1.6) and 1.0 (0.9-1.2) for IHD. In the case-control study, corresponding multifactorially adjusted odds ratios for IHD/coronary atherosclerosis were 0.5 (0.2-1.3) and 1.2 (1.0-1.5). These genotypes were not associated with risk of asthma or COPD. Leukotriene C4 synthase promoter genotypes influence risk of TIA and ischemic stroke, but not risk of IHD/coronary atherosclerosis, asthma, or COPD.
缺血性心血管疾病和阻塞性肺疾病都涉及炎症。白三烯可能是重要的促炎介质。我们检验了以下假设：白三烯C4合酶的（-1072）G＞A和（-444）A＞C启动子多态性会增加短暂性脑缺血发作（TIA）、缺血性中风、缺血性心脏病（IHD）、哮喘和慢性阻塞性肺疾病（COPD）的发病风险。我们对丹麦普通人群、哥本哈根城市心脏研究中的个体以及丹麦IHD/冠状动脉粥样硬化患者（哥本哈根缺血性心脏病研究）进行了基因分型。我们采用了前瞻性研究（n = 10386）、横断面研究（n = 10386）和病例对照研究（n = 2392 + 5012）设计。（-1072）A的等位基因频率为0.07，（-444）C的等位基因频率为0.29。（-1072）AA基因型的TIA累积发病率高于GG基因型（对数秩检验：p＜0.001），而（-444）CC基因型的TIA累积发病率低于AA基因型（对数秩检验：p = 0.03）。（-444）CC基因型的缺血性中风累积发病率也低于AA基因型（对数秩检验：p = 0.04）。TIA的多因素调整风险比，（-1072）AA基因型与GG基因型相比为5.2（95%CI：1.9 - 14），（-444）CC基因型与AA基因型相比为0.4（0.2 - 1.0）。缺血性中风的相应值分别为1.9（0.7 - 5.2）和0.7（0.5 - 1.0），IHD的相应值分别为0.8（0.4 - 1.6）和1.0（0.9 - 1.2）。在病例对照研究中，IHD/冠状动脉粥样硬化的相应多因素调整比值比分别为0.5（0.2 - 1.3）和1.2（1.0 - 1.5）。这些基因型与哮喘或COPD的发病风险无关。白三烯C4合酶启动子基因型影响TIA和缺血性中风的发病风险，但不影响IHD/冠状动脉粥样硬化、哮喘或COPD的发病风险。
