Methylenetetrahydrofolate reductase gene polymorphism in coronary artery disease patients

Coronary artery disease occurs with the interact ion between environmental influences and genetic factors. Genetic susceptibility may be caused by mutations and polymorphisms in a variety of genes mainly involved in blood coagulation, metabolism of lipids, homocysteine and or iron. The most common form of genetic hyperhomocysteinemia results from the production of a thermolabile variant of methylene tetrahydrofolate reductase [MTHFR] with reduced enzymatic activity. This study was performed on ninety individuals selected with normal serum glucose, kidney, liver, and thyroid function test and lipid profile. They classified into: Group I: 27 apparently healthy persons as control group. Group II: 3 apparently healthy persons with elevated homocysteine level. Group III: 27 CAD patients with normal coronary angiography. Group IV: 33 CAD patients with abnormal coronary angiography. The following specific investigations were done for all the studied persons:- Serum homocysteine [Hcy], serum folic acid [FA] and MTHFR genotyping by PCR-RFLP

Results: In group III three patients had elevated Hey [11.1%]. There was significant elevation of Hey level in group IV compared to group I [P<0. 05].however there were insignificance differences in mean value of folic acid of the studied groups compared to each other. As regard the relation between the MTHFR polymorphisam and hey and FA levels, in group I there was significant elevation of serum Hey level in carriers of CT genotype compared to carriers of CC genotype [P<0.05]. Homocysteine level was highly elevated in patients had TT genotype in group III and group IV when compared to CC and CT genotypes and this was statistically highly significant [<0.000] in group IV, but insignificant elevation in group III Folic acid level was not differing between patients had TT genotype when compared to CC and CT genotype in all studied groups and that was statistically insignificant. When we study the severity of CAD in group IV there was insignificant elevation of serum Hey level in group of one vessel affection compared to group of two vessel and multi vessel affection, there was Significant elevation of serum Hey level in group of >/= 90% stenosis compared to group of >50-75% stenosis and 75-90% stenosis. However there was insignificant difference in serum FA between the groups compared to each other. Homozygous TT was detected in group of one vessel affection and with >90% stenosis. Carriers of TT genotypes in group of one vessel affection and in>/= 90% stenosis had highly significant elevation [P<0.000] of serum homocysteine compared to CC and CT genotypes in the same group

Conclusion: Our findings support that homozygous MTHFR TT genotype is a genetic risk factor for CAD

Homozygous VN (677C to T) and d/D (2756G to A) variants in the methylenetetrahydrofolate and methionine synthase genes in a case of hyperhomocysteinemia with stroke at young age

Hyperhomocysteinemia is known to be associated with an increased risk of myocardial infarction, stroke, peripheral arterial disease, and venous thrombosis. Gene polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) may account for reduced enzyme activity and hyperhomocysteinemia. A recent study has documented evidence of polygenic regulation of plasma homocyteine. We report here on a case of occlusive stroke at young age and hyperhomocysteinemia with homozygous VN (677C to T) variant in the MTHFR gene as well as homozygous D/D (2756G to A) variant in the MS gene.