Clinical Investigations: Acute Ischemic Heart Disease
Association of a novel single nucleotide polymorphism of the prostacyclin synthase gene with myocardial infarction*,**,

https://doi.org/10.1067/mhj.2002.122171Get rights and content

Abstract

Background Myocardial infarction (MI) is a complex multifactorial and polygenic disorder that is thought to result from an interaction between an individual's genetic makeup and various environmental factors. The purpose of this study was to investigate the association between a novel single nucleotide polymorphism in the prostacyclin synthase gene and MI. Methods and Results By the use of polymerase chain reaction-single-strand conformation polymorphism analysis, we identified a single nucleotide polymorphism, C1117A, in exon 8. This nucleotide change did not cause an amino acid change in codon 373. We performed an association study of the polymorphism in 138 patients and 130 healthy control subjects. Multiple logistic linear regression analysis showed the genotype distributions were significantly different between the control group and the MI group (odds ratio, 2.12; 95% CI, 1.47-3.05, P =.04). The C/C genotype was found more frequently in the MI group than in the control group. Conclusions We conclude that the C1117A polymorphism in exon 8 is associated with risk for MI and may be a genetic marker of MI in Japanese persons. (Am Heart J 2002;143:797-801.)

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).

. A, Nucleotide and amino acid sequences around novel polymorphism in exon 8 of the prostacyclin synthase gene. B, Restriction fragment length polymorphism analysis for determination of genotype. The C/C genotype shows a single band of 175 bp. The

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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    *

    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.

    **

    Reprint requests: Tomohiro Nakayama, MD, Division of Receptor Biology, Advanced Medical Research Center, Ooyaguchi-kamimachi 30-1, Itabashi-ku, Tokyo 173-8610, Japan.

    E-mail: [email protected]

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