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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:193.)
© 2002 American Heart Association, Inc.

Letters to the Editor

The T Allele of The C⁶⁷⁷T 5,10-Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphism May Protect Endothelial Function in Young, Normal Subjects

Rob Butler; Andrew D. Morris; Allan D. Struthers

University Department of Clinical Pharmacology and Therapeutics (R.B., A.D.S),, University Department of Medicine (A.D.M.) and The Diabetes Centre (A.D.M.), Ninewells Hospital and Medical School, Dundee,, United Kingdom

To the Editor:

There is a modest amount of data suggesting hyperhomocysteinemia may be a determinant of vascular diseases such as stroke¹ and myocardial infarction.² However, this finding has not been confirmed in longitudinal studies,^{3 4} and this has led to the suggestion by Evans et al³ that higher homocysteine levels may be an effect of vascular disease rather than the cause of it. A recent meta-analysis suggests that the MTHFR genotype leads to mild hyperhomocysteinemia but not to vascular disease⁵ and may be an epiphenomena as the result of an association with other risk factors such as male sex, hypertension, smoking, hyperlipidemia, and reduced renal clearance.

Hyperhomocysteinemia can result from either genetic or nutritional causes. The MTHFR gene controls the remethylation of homocysteine to methionine and has been reported to cause mild hyperhomocysteinaemia.⁶ Case control studies have reported an association among the MTHFR polymorphism, cardiovascular disease, and myocardial infarction.^{7 8} However, the association is also inconclusive as others have reported no link between the genotype and cardiovascular events.⁹ This gained further support when Demuth et al¹⁰ demonstrated opposite effects of hyperhomocysteinemia and the MTHFR C⁶⁷⁷T mutation, showing that homocysteine positively correlated with carotid lumen diameter and TT homozygotes negatively correlated with lumen diameter. Similarly, there was no link between the MTHFR genotype and homocysteine level in this study. One way to help clarify whether a possible culprit is a cause of vascular disease, or a result of it, is to study young men before any overt vascular disease has occurred.

In this report, . . . [Full Text of this Article]

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