Recurrent Myocardial Infarction Despite Normal C-reactive Protein in a Patient with Behcet’s Disease and Compound Heterozygous Methylenetetrahydrofolate Reductase (MTHFR) Mutations (C677T and A1298C)

Abstract

A 39-year-old diabetic female with Behcet’s disease presented with acute inferior wall myocardial infarction and underwent successful angioplasty of the occluded circumflex artery with a bare-metal stent (balancing increased the bleeding risk with Behcet's). Other coronary vessels were free of obstructive atherosclerosis. Optimal coronary artery disease (CAD) therapy was commenced, and Behcet’s disease treatment was intensified with the normalization of C-reactive protein. Two years later, she presented with an acute left anterior descending artery occlusion that was managed with a drug-eluting stent this time. There was no evidence of diffuse atherosclerosis on coronary angiogram or coronary calcifications on the chest computed tomography (CT) scan. Compound heterozygous methylenetetrahydrofolate reductase (MTHFR) mutations (C677T and A1298C) and high-normal plasma homocysteine were detected. With the long-term continuation of dual anti-platelet, lipid-lowering, immunosuppressive, and folic-acid therapies, she did not have cardiac events during the three-year follow-up. This is the first report of recurrent thrombotic acute coronary syndrome (ACS) in a patient with diabetes, compound heterozygous MTHFR mutations, Behcet’s disease with normal C-reactive protein (CRP), and no evidence of diffuse coronary artery disease.

The Correlation of MTHFR SNPs, Homocysteine, and Conventional Risk Predictors with Coronary Artery Disease

“…The most studied SNP in MTHFR gene, the C677T (rs1801133, where alanine residue is changed to valine) is associated with elevated homocysteine levels and higher risk of CAD [2,18,19,38]. The A1298C SNP (rs1801131) in MTHFR gene has disparate association with homocysteine levels and CAD, as some studies show positive [18,22,42] and others negative association for disease causation [38,40]. The current study displayed strong relation of MTHFR SNPs with CAD; ANOVA analysis for rs1801133 had significance with CAD (p = 0.008) and in control vs. cases (p = 0.010).…”