Clinical Investigations: Acute Ischemic Heart DiseaseAssociation of a novel single nucleotide polymorphism of the prostacyclin synthase gene with myocardial infarction*,**,★
Section snippets
Subjects
The study population included 130 healthy control subjects and 138 patients with MI who were aged <70 years (Table I).All subjects who agreed to participate in the study were evaluated on the basis of a detailed questionnaire that provided information about coronary risk factors such as smoking habits and presence of diabetes mellitus or hypertension. History of MI was confirmed by the presence of 2 or more of the following: history of the chest pain indicative of MI, creatine kinase and
Results
Using SSCP, we identified a single nucleotide polymorphism (SNP) in which cytosine was substituted for adenine at nucleotide 1117. This nucleotide change does not change the amino acid at codon 373 in exon 8 of the prostacyclin synthase gene (Figure 1).
Discussion
Cardiovascular disease including MI is multifactorial, with complex interactions existing between genetic and environmental components.1, 2 In general, the incidence of MI increases as a function of the number of conventional risk factors.2 Some individuals with MI, however, do not exhibit any conventional risk factors, which suggests the contribution of genetic factors.
Since the discovery of prostacyclin, an antiaggregatory factor, arterial thrombosis resulting from platelet aggregates has
Acknowledgements
We thank Dr Y. Watanabe and Dr Y. Izumi for collecting samples, and Ms H. Tobe for technical assistance.
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Cited by (52)
Interactions among Variants in Eicosanoid Genes Increase Risk of Atherothrombotic Stroke in Chinese Populations
2017, Journal of Stroke and Cerebrovascular DiseasesVariants in COX-2, PTGIS, and TBXAS1 Are Associated with Carotid Artery or Intracranial Arterial Stenosis and Neurologic Deterioration in Ischemic Stroke Patients
2017, Journal of Stroke and Cerebrovascular DiseasesCitation Excerpt :In contrast, in the Atherosclerosis Risk in Communities study and one other study, the C allele was reported to be associated with higher risk of stroke in African Americans or Brazilian population.23,24 Rs5629, a synonymous SNP in exon 8, was associated with MI in a Japanese population,25 and the number of tandem repeats in the promoter region was associated with cerebral infarction.26 The association of TBXAS1 variation with cardiovascular disease and IS has not been reported.
Analysis of genetic polymorphism and biochemical characterization of a functionally decreased variant in prostacyclin synthase gene (CYP8A1) in humans
2015, Archives of Biochemistry and BiophysicsCitation Excerpt :PGI2 counteracts platelet-derived thromboxane A2 (TXA2) and the balance and regulation of these two prostanoids are important in blood hemostasis [12–14]. Multiple studies have reported that genetic variations of CYP8A1 affect PGI2 levels in blood, and these altered variations have been suggested to be associated with an increased risk for cardiovascular diseases such as myocardial infarction (MI) [15,16], cerebral infarction (CI) [17], and essential hypertension (EH) [18–20]. For example, in a family study, three individuals were identified to have a CYP8A1 variant, a heterozygous splicing mutation in the CYP8A1 gene, resulting in a truncated CYP8A1 protein without enzyme activity [19].
Effect of single nucleotide polymorphisms of the prostacyclin receptor gene on platelet activation in Japanese healthy subjects and patients with cerebral infarction
2013, Journal of Clinical NeuroscienceCitation Excerpt :In particular, subjects with the C/C genotype are at greater risk for CI (p < 0.001). Nakayama et al.28 have previously reported that the C1117A polymorphism in exon 8 of the prostacyclin synthase gene is associated with an increased risk of myocardial infarction (MI) and may be a genetic marker for MI. However, this SNP should not directly affect the expression or function of prostacyclin synthase, because it does not cause any change to the amino acid encoded by codon 373.
Haplotype study of the CYP4A11 gene and coronary artery disease in Han and Uygur populations in China
2013, GeneCitation Excerpt :Mounting evidence has demonstrated that CYP enzymes are involved in the pathogenesis of CAD. Polymorphisms of CYP genes e.g., CYP1B1 (metabolize tobacco-smoke polycyclic aromatic hydrocarbons and 17-beta-estradiol) (Kaur-Knudsen et al., 2009), CYP2C8 (synthesis of epoxyeicosatrienoic acid (EET)) (Rodenburg et al., 2010), CYP2C19 (involved in clopidogrel metabolism) (Sofi et al., 2011), CYP3A4 (main metabolic enzyme of fentanyl) (He et al., 2011), CYP4F2 (synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE)) (Munshi et al., 2012), CYP8A (prostacyclin synthesis) (Nakayama et al., 2002), CYP11B2 (aldosterone synthesis) (Munshi et al., 2010), CYP17 and CYP19 (synthesis of sex hormones), have been demonstrated to have a relationship with CAD (Letonja et al., 2005). In humans, CYP4A11 (cytochrome P450, family 4, subfamily A, polypeptide 11) converts arachidonic acid to 20-HETE, which has a crucial role in the modulation of cardiovascular homeostasis.
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Supported by a grant from the Ministry of Education, Science and Culture of Japan (High-Tech Research Center, Nihon University), a research grant from an alumni association of Nihon University School of Medicine, Tanabe Biomedical Conference, and the Toray-Yamanouchi Pharmacology Company, Japan.
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Reprint requests: Tomohiro Nakayama, MD, Division of Receptor Biology, Advanced Medical Research Center, Ooyaguchi-kamimachi 30-1, Itabashi-ku, Tokyo 173-8610, Japan.
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E-mail: [email protected]