This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kosokabe, T. Articles by Hayakawa, T. Search for Related Content PubMed PubMed Citation Articles by Kosokabe, T. Articles by Hayakawa, T. Related Collections Restenosis

(Circulation. 2001;103:2048.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Relation of a Common Methylenetetrahydrofolate Reductase Mutation and Plasma Homocysteine With Intimal Hyperplasia After Coronary Stenting

Tai Kosokabe, MD; Kenji Okumura, MD; Takahito Sone, MD; Junichiro Kondo, MD; Hideyuki Tsuboi, MD; Hiroaki Mukawa, MD; Takahito Tomida, MD; Tomomichi Suzuki, MD; Hiroki Kamiya, MD; Hideo Matsui, MD; Tetsuo Hayakawa, MD

From Internal Medicine II, Nagoya University School of Medicine (T.K., K.O., T.T., T. Suzuki, H.K., H. Matsui, T.H.), Nagoya, Japan; and Department of Cardiology (T. Sone, J.K., H.T., H. Mukawa), Ogaki Municipal Hospital, Ogaki, Japan.

Background—Hyperhomocysteinemia has been identified as an independent risk factor for coronary artery disease. Recent studies have shown that a common mutation (nucleotide 677 CT) in the methylenetetrahydrofolate reductase (MTHFR) gene may contribute to mild hyperhomocysteinemia and, therefore, to the incidence of coronary artery disease. No information exists, however, regarding the association between the mutation of the MTHFR gene or plasma homocysteine levels and morphological analysis of coronary atherosclerosis using intravascular ultrasound.

Methods and Results—To examine the potential influence of MTHFR genotype and homocysteine on coronary arteries morphologically, we screened 62 patients with 65 lesions that were treated with 93 Palmaz-Schatz stents. The plasma homocysteine levels in the patients with the TT genotype were not significantly higher than those in the patients with non-TT (CC+CT) genotypes (13.1±5.5 versus 11.5±3.1 mmol/L, P=0.16). Angiographic analysis showed that the percent diameter stenosis in the patients with the TT genotype was significantly greater than that in those with non-TT genotypes (43.7±17.8% versus 29.0±22.0%, P=0.015). Intravascular ultrasound analysis showed that the TT genotype was significantly associated with greater intimal hyperplasia area (5.70±1.94 versus 3.72±1.38 mm², P=0.001). In multiple stepwise regression analysis, the number of the T alleles was the only independent predictor of intimal hyperplasia after intervention (r²=0.21, P=0.004).

Conclusions—The homozygous mutant genotype of the MTHFR gene may increase the risk of in-stent restenosis more than does the normal homozygous or heterozygous genotype.

Key Words: angiography • genes • restenosis • stents • ultrasonics

This article has been cited by other articles:

				G. De Luca, H. Suryapranata, G. Gregorio, H. Lange, and M. Chiariello Homocysteine and Its Effects on In-Stent Restenosis Circulation, November 8, 2005; 112(19): e307 - e311. [Full Text] [PDF]

				H. Lange, H. Suryapranata, G. De Luca, C. Borner, J. Dille, K. Kallmayer, M. N. Pasalary, E. Scherer, and J.-H. E. Dambrink Folate Therapy and In-Stent Restenosis after Coronary Stenting N. Engl. J. Med., June 24, 2004; 350(26): 2673 - 2681. [Abstract] [Full Text] [PDF]

				W. Koch, G. Ndrepepa, J. Mehilli, S. Braun, M. Burghartz, H. Lengnick, K. Kolling, A. Schomig, and A. Kastrati Homocysteine Status and Polymorphisms of Methylenetetrahydrofolate Reductase Are Not Associated With Restenosis After Stenting in Coronary Arteries Arterioscler. Thromb. Vasc. Biol., December 1, 2003; 23(12): 2229 - 2234. [Abstract] [Full Text] [PDF]

				G. Schnyder, Y. Flammer, M. Roffi, R. Pin, and O. M. Hess Plasma homocysteine levels and late outcome after coronary angioplasty J. Am. Coll. Cardiol., November 20, 2002; 40(10): 1769 - 1776. [Abstract] [Full Text] [PDF]

				H. C. Lowe, S. N. Oesterle, and L. M. Khachigian Coronary in-stent restenosis: Current status and future strategies J. Am. Coll. Cardiol., January 16, 2002; 39(2): 183 - 193. [Abstract] [Full Text] [PDF]