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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:298-302.)
© 1999 American Heart Association, Inc.

Original Contributions

Polymorphism of the Methionine Synthase Gene

Association With Homocysteine Metabolism and Late-Onset Vascular Diseases in the Japanese Population

Hiroyuki Morita; Hiroki Kurihara; Takao Sugiyama; Chikuma Hamada; Yukiko Kurihara; Takayuki Shindo; Yoshio Oh-hashi; Yoshio Yazaki

From the Departments of Cardiovascular Medicine (H.M., H.K., Y.K., T.S., Y.O.-h., Y.Y.) and of Pharmacoepidemiology (C.H.), Graduate School of Medicine, University of Tokyo, and the Institute for Adult Diseases, Asahi Life Foundation (T.S.), Tokyo, Japan.

Correspondence to Hiroki Kurihara, MD, Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail kuri-tky{at}umin.ac.jp

Abstract—Methionine synthase and 5,10-methylenetetrahydrofolate reductase (MTHFR) sequentially catalyze the remethylation of homocysteine to methionine. A point mutation in the encoding region of the methionine synthase gene, which results in substitution of an aspartic acid for a glycine residue (D919G), has been identified in patients of the cblG genetic complementation group; these patients exhibit significantly decreased methionine synthase activity. Nevertheless, the D919G mutation has also been reported to be common in the general population. In this study, we analyzed the distribution of methionine synthase D/G polymorphism in the Japanese population and examined the extent to which it is associated with altered homocysteine metabolism and late-onset vascular diseases. We studied 215 patients with coronary artery disease, 251 patients with histories of ischemic stroke, and 257 control subjects. The methionine synthase genotype was analyzed by polymerase chain reaction followed by HaeIII digestion; allele frequencies for the D919G variant of the enzyme proved to be similar in all 3 subject groups (control subjects, 0.17; coronary artery disease patients, 0.17; and ischemic stroke patients, 0.19). Furthermore, in patients with ischemic stroke, plasma levels of homocyst(e)ine and folate were similar, irrespective of methionine synthase genotype. Thus, the methionine synthase D919G mutation was found to be common in the Japanese general population, and it appears unlikely that this polymorphism has a major effect on homocysteine metabolism and/or the onset of vascular diseases.

Key Words: homocysteine • methionine synthase • methylenetetrahydrofolate reductase • genetics

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