Leukotriene C4 synthase and ischemic cardiovascular disease and obstructive pulmonary disease in 13,000 individuals.
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.
Freiberg
Jacob J
JJ
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark.
Dahl
Morten
M
Tybjaerg-Hansen
Anne
A
Grande
Peer
P
Nordestgaard
Børge G
BG
D000328:Adult; D001249:Asthma / Q000150:complications / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D015994:Incidence; D002546:Ischemic Attack, Transient / Q000150:complications / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D008173:Lung Diseases, Obstructive / Q000150:complications* / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications* / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics; D020521:Stroke / Q000150:complications / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics
D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase