Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease.

J.J. Freiberg; A. Tybjaerg-Hansen; H. Sillesen; Gorm Boje Jensen; Børge Nordestgaard; Jacob J Freiberg; Anne Tybjærg-Hansen; Henrik Sillesen; Gorm B Jensen; Børge G Nordestgaard

doi:10.1161/ATVBAHA.107.158873

Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease.

J.J. Freiberg, A. Tybjaerg-Hansen, H. Sillesen, Gorm Boje Jensen, Børge Nordestgaard, Jacob J Freiberg, Anne Tybjærg-Hansen, Henrik Sillesen, Gorm B Jensen, Børge G Nordestgaard

26 Citations (Scopus)

Abstract

OBJECTIVE: 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. METHODS AND RESULTS: 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. CONCLUSIONS: Leukotriene C(4) synthase -1072 AA genotype predict increased risk, whereas -444 CC genotype predict decreased risk of ischemic cerebrovascular disease.

Original language	English
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	28
Issue number	5
Pages (from-to)	990-6
Number of pages	6
ISSN	1079-5642
DOIs	https://doi.org/10.1161/ATVBAHA.107.158873 https://doi.org/10.1161/ATVBAHA.107.158873
Publication status	Published - 2008

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Freiberg, J. J., Tybjaerg-Hansen, A., Sillesen, H., Jensen, G. B., Nordestgaard, B., Freiberg, J. J., Tybjærg-Hansen, A., Sillesen, H., Jensen, G. B., & Nordestgaard, B. G. (2008). Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 28(5), 990-6. https://doi.org/10.1161/ATVBAHA.107.158873, https://doi.org/10.1161/ATVBAHA.107.158873

Freiberg, JJ, Tybjaerg-Hansen, A , Sillesen, H, Jensen, GB, Nordestgaard, B, Freiberg, JJ, Tybjærg-Hansen, A, Sillesen, H, Jensen, GB & Nordestgaard, BG 2008, 'Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease.', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 5, pp. 990-6. https://doi.org/10.1161/ATVBAHA.107.158873, https://doi.org/10.1161/ATVBAHA.107.158873

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title = "Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease.",

abstract = "OBJECTIVE: 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. METHODS AND RESULTS: 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. CONCLUSIONS: Leukotriene C(4) synthase -1072 AA genotype predict increased risk, whereas -444 CC genotype predict decreased risk of ischemic cerebrovascular disease.",

author = "J.J. Freiberg and A. Tybjaerg-Hansen and H. Sillesen and Jensen, {Gorm Boje} and B{\o}rge Nordestgaard and Freiberg, {Jacob J} and Anne Tybj{\ae}rg-Hansen and Henrik Sillesen and Jensen, {Gorm B} and Nordestgaard, {B{\o}rge G}",

year = "2008",

doi = "10.1161/ATVBAHA.107.158873",

language = "English",

volume = "28",

pages = "990--6",

journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",

issn = "1079-5642",

publisher = "Lippincott Williams & Wilkins",

number = "5",

}

TY - JOUR

T1 - Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease.

AU - Freiberg, J.J.

AU - Tybjaerg-Hansen, A.

AU - Sillesen, H.

AU - Jensen, Gorm Boje

AU - Nordestgaard, Børge

AU - Freiberg, Jacob J

AU - Tybjærg-Hansen, Anne

AU - Sillesen, Henrik

AU - Jensen, Gorm B

AU - Nordestgaard, Børge G

PY - 2008

Y1 - 2008

N2 - OBJECTIVE: 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. METHODS AND RESULTS: 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. CONCLUSIONS: Leukotriene C(4) synthase -1072 AA genotype predict increased risk, whereas -444 CC genotype predict decreased risk of ischemic cerebrovascular disease.

AB - OBJECTIVE: 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. METHODS AND RESULTS: 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. CONCLUSIONS: Leukotriene C(4) synthase -1072 AA genotype predict increased risk, whereas -444 CC genotype predict decreased risk of ischemic cerebrovascular disease.

U2 - 10.1161/ATVBAHA.107.158873

DO - 10.1161/ATVBAHA.107.158873

M3 - Journal article

C2 - 18276912

SN - 1079-5642

VL - 28

SP - 990

EP - 996

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

IS - 5

ER -

Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease.

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