Vol. 81, September 2013

Relation between Methylenetetrahydrofolate Reductase C677T Gene Polymorphism, Hyperhomocysteinemia and Coronary Artery Disease

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Relation between Methylenetetrahydrofolate Reductase C677T Gene Polymorphism, Hyperhomocysteinemia and Coronary Artery Disease, KHADIGA A. ABDEL MAGEED, MADEEHA Y. BAKHEET, EBTSAM F. MOHAMMED, HAMDY S. MOHAMMED, OMNIA A. MOHAMMED, OLA A. AFIFY, HEBA A. ABDEL-HAFEZ, AMAL M. ABDEL-AAL and ZEINAB A. ABDEL-HAMED

 

Abstract
Background and Aim: Hyperhomocysteinemia is known to be a risk factor for coronary artery disease (CAD). The most common form of genetic hyperhomocysteinemia results from the production of a variant of methylenetetrahydrofolate reductase (MTHFR) with reduced enzymatic activity. This study aimed to investigate the distribution of MTHFR geno-types in CAD patients and apparently healthy individuals and the role of this gene polymorphism as a risk factor for CAD and as a predictor of its severity.
Patients and Methods: The study included sixty CAD patients (27 with normal and 33 with abnormal coronary angiography) and thirty apparently healthy individuals as a control group after exclusion of smoking, hypertension, diabetes, thyroid dysfunction, dyslipidemia, and liver and kidney diseases. MTHFR genotyping was performed by PCR-RFLP. Measurement of serum homocysteine (Hcy) and folic acid (FA) levels were done for all patients and controls.
Results: Elevated Hcy levels were found in three appar-ently healthy persons so, they were excluded from the control group. There was significant elevation of Hcy level in CAD patients with abnormal angiography compared to control group (p<0.05). Lower frequency of CC genotype carriers was found in CAD patients groups in comparison with control group. CT genotype was detected in 33.4% of the control group, 33.3% of CAD patients with normal angiography and 57.6% of patients with abnormal angiography. Except for the three persons with high Hcy levels, no one of the apparently healthy subjects had TT genotype. However, this genotype was detected in 14.8% of CAD patients with normal angiog-raphy and 15.2% of patients with abnormal angiography. In CAD patients with abnormal angiography, TT genotype carriers had elevated Hcy levels compared to those carrying CC and CT genotypes (p<0.000). There was significant elevation of serum Hcy level in patients with stenosis 90% compared to those with stenosis >50-75% and 75-90%. However, there was insignificant difference in serum FA levels between all the studied groups with different classifications. Homozygous TT genotype was detected in all patients with one vessel affection and all patients with 90% stenosis. These patients had highly significant elevation of serum Hcy compared to CC and CT genotypes in the same respective group (p<0.000).
Conclusion: CC is the commonest genotype of MTHFR gene polymorphism in healthy individuals and patients with normal angiography and CT is the commonest one in those with abnormal angiography. TT genotype was associated with elevated homocysteine levels and so higher CAD risk. It is also associated with marked degree of stenosis in coronary vessels.

 

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