Relation of a common methylenetetrahydrofolate reductase mutation and plasma homocysteine with intimal hyperplasia after coronary stenting

• Published in: Circulation (New York, N.Y.) Vol. 103; no. 16; pp. 2048 - 2054
• Main Authors: KOSOKABE, Tai, OKUMURA, Kenji, HAYAKAWA, Tetsuo, SONE, Takahito, KONDO, Junichiro, TSUBOI, Hideyuki, MUKAWA, Hiroaki, TOMIDA, Takahito, SUZUKI, Tomomichi, KAMIYA, Hiroki, MATSUI, Hideo
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 24-04-2001; American Heart Association, Inc
• Subjects: Alleles; Angioplasty, Balloon, Coronary - adverse effects; Biological and medical sciences; Coronary Artery Disease - blood; Coronary Artery Disease - surgery; Coronary Restenosis - blood; Coronary Restenosis - diagnostic imaging; Coronary Restenosis - genetics; Disease Progression; Diseases of the cardiovascular system; DNA Mutational Analysis; Female; Follow-Up Studies; Genotype; Homocysteine - blood; Homozygote; Humans; Hyperplasia - blood; Hyperplasia - diagnostic imaging; Hyperplasia - etiology; Male; Medical sciences; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Multivariate Analysis; Mutation; Oxidoreductases Acting on CH-NH Group Donors - genetics; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Risk; Stents - adverse effects; Tunica Intima - diagnostic imaging; Tunica Intima - surgery; Ultrasonography, Interventional; Vascular Patency - genetics; Methylenetetrahydrofolate reductase (NADPH); Pathogenesis; Hyperplasia; Cardiovascular disease; Genetic determinism; Stent; Arterial disease; Vascular disease; Gene; Intima; Complication; Sonography; Human; Endoprosthesis; Thiol; Enzyme; Coronary artery; Instrumentation therapy; Genotype; Endovascular route; Coronary heart disease; Sulfur containing aminoacid; Restenosis; Phenotype; Risk factor; Oxidoreductases; Mutation
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.103.16.2048

Hyperhomocysteinemia has been identified as an independent risk factor for coronary artery disease. Recent studies have shown that a common mutation (nucleotide 677 C-->T) 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.
To examine the potential influence of MTHFR genotype and homocysteine on coronaryarteries 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).
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.